Pesticides

ABSTRACT

New insecticides are of formula: ##STR1## wherein R 1  represents hydrogen or a methyl group; R 2  represents hydrogen or a halogeno or lower alkyl group; R 3  represents hydrogen or a halogeno or carbo(lower alkoxy) group which contains at least 2 carbon atoms in the lower alkoxy residue when R 2  represents methyl; with the proviso that (a) R 2  and R 3  each represent hydrogen only when R 1  represents methyl, (b) when R 1  and R 3  each represent hydrogen and R 2  represents alkyl, that alkyl group contains at least 2 carbon atoms and (c) when R 3  represents halogeno, R 2  represents hydrogen or halogeno; and R represents a group which forms insecticidal esters with chrysanthemic acid e.g. 5-benzyl-3-furylmethyl, 3-phenoxybenzyl, α-cyano-3-phenoxybenzyl. The esters are prepared by forming the ester linkage conventionally or by a Wittig reaction using a 3-formyl- or 3-acetyl-2,2-dimethyl cyclopropane carboxylic acid esterified with the desired residue or by an alkyl group which is subsequently converted to the desired residue.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of our earlier copending application Ser. No. 764,895 filed Feb. 2, 1977, now abandoned, which in turn is a division of our earlier application Ser. No. 497,056 filed Aug. 13, 1974, now U.S. Pat. No. 4,024,163, which in turn is a continuation-in-part of our earlier copending application Ser. No. 363,318 filed May 24, 1973, now abandoned. This application is also a continuation-in-part of our earlier application Ser. No. 40,304 filed May 18, 1979, now abandoned, and our earlier application Ser. No. 962,025 filed Nov. 20, 1978, also now abandoned.

This invention relates to pesticides and more particularly to synthetic insecticides of the pyrethrin type, to their preparation, to compositions containing them and to the pesticidal use of the compounds and compositions.

For many years, research has been pursued in the field of synthetic analogues of the pyrethrins to discover synthetic substitutes having properties superior to those of the natural products. Ideally, synthetic analogues of the naturally occurring pyrethrins should compare well with or be superior to the natural products as regards level of toxicity to pests and mammals, pesticidal spectrum and known-down properties and, in addition, should offer ease of manufacture.

Since the discovery that the naturally occurring pyrethrins were esters of certain substituted cyclopropane carboxylic acids and substituted cyclopentenolones, the search for synthetic analogues concentrated initially on modifying the "alcohol" part of the ester molecule and later on modifying the "acid" part of the ester molecule or, in some cases, modifying both parts of the ester molecule. The naturally occurring esters are esters of chrysanthemic or pyrethric acids of the formula: ##STR2## where X represents a methyl group (chrysanthemic acid) or a carbomethoxy group (pyrethric acid).

We have now found that a high level of insecticidal activity and a particularly valuable combination of properties for controlling insects and other pests can be obtained in esters of 2,2-dimethyl-3-alkenyl cyclopropane carboxylic acid where the substitution on the 3-alkenyl side chain differs from that of all previously known pyrethrin-like esters, having high insecticidal activity and low mammalian toxicity. Certain esters of the invention also have exceptionally good photo stability.

Accordingly, the present invention provides esters of the general formula: ##STR3## wherein R¹ represents hydrogen or a methyl group; R² represents hydrogen or a halogeno or alkyl group; R³ represents hydrogen or a halogeno or carboalkoxy group, said carboalkoxy group containing at least 2 carbon atoms in the alkoxy residue when R² represents methyl; with the proviso that (a) R² and R³ each represent hydrogen only when R¹ represents methyl, (b) when R¹ and R³ each represent hydrogen and R² represents alkyl, that alkyl group contains at least 2 carbon atoms and (c) when R³ represents halogeno, R² represents hydrogen or halogeno; and R represents (a) hydrogen (or a salt or acid halide derivative of the acid) or an alkyl group, or (b) a group of formula: ##STR4## wherein Z represents O, S, CH₂ or Co, Y represents hydrogen or an alkyl, alkenyl or alkynyl group or an aryl or furyl group which is unsubstituted or substituted in the ring by one or more alkyl, alkenyl, alkoxy or halogeno groups, R⁷ and R⁸, which may be the same or different, each represent hydrogen or an alkyl, or alkenyl group, R⁹ represents hydrogen or a methyl group, R¹⁰ and R¹¹, which may be the same or different, each represent hydrogen or an allyl group, R¹² represents an organic radical having carbon-carbon unsaturation in a position α to the CH₂ group to which R¹² is attached, A/S indicates an aromatic ring or a dihydro or tetrahydro analogue thereof, X¹, X², X³ and X⁴, which may be the same or different, each represent hydrogen, chlorine or a methyl group, Z³ represents --CH₂ -- or --O-- or --S-- or --CO--, D represents H, CN or --C.tbd.CH, Z¹ and Z², which may be the same or different, each represent chlorine or a methyl group and n=0, 1 or 2, with the proviso that R does not represent hydrogen (or an acid chloride derivative of the acid) or an ethyl or allethronyl group when R¹ represents hydrogen, R² and R³ each represent chlorine and the compound is racemic, and with the proviso that when R¹ represents hydrogen and R² and R³ each represent halogen, R does not represent a 5-benzyl-3-furylmethyl, α-cyano-5-benzyl-3-furylmethyl, 3-phenoxy-benzyl, or an α-cyano-3-phenoxy-benzyl group.

The esters of the present invention where R represents a group of formula III, IV, V, VI, VIA or VIB are insecticidal esters having a valuable combination of properties for controlling insects and other pests.

The esters of the present invention where R represents alkyl are not insecticidal but are useful intermediates in the production of the insecticidal esters e.g. by transesterification. As will be discussed in more detail below, the new alkyl esters of the present invention can be prepared in that form by a Wittig synthesis and it is not necessary to convert the alkyl ester into the free carboxylic acid in order to produce the insecticidal esters of the invention. However, if desired, the alkyl esters can be converted into the free carboxylic acid, e.g. by hydrolysing the ester to give a salt and subsequently acidifying the salt.

The esters of the present invention where R represents alkyl and R³ =carboalkoxy are useful intermediates in the production of the insecticidal esters which can be converted by acid catalysis, e.g. using toluene-4-sulphonic acid in benzene, to the corresponding free carboxylic acid without affecting the carboalkoxy group R³. As will be discussed in more detail below, the new alkyl esters of the present invention are prepared in that form by a Wittig synthesis and it is necessary to convert the alkyl ester into the free carboxylic acid in order to produce the insecticidal esters of the invention. This is best achieved selectively utilising a t-butyl ester (R=t-butyl). However, if desired, a t-butyl or other alkyl ester can be converted into the free carboxylic acid, by partial saponification but it is difficult to prevent saponification of the carboalkoxy group R³ at the same time.

The insecticidal esters of the present invention may be regarded structurally as esters of a 3-substituted-2,2-dimethylcyclopropane carboxylic acid and an alcohol e.g. a benzyl alcohol, a furylmethyl alcohol, a cyclopentenolone or an α-cyano- or α-ethynyl-benzyl or α-cyano- or α-ethynyl-furylmethyl alcohol. While the esters may be conveniently described structurally in these terms, it will be appreciated and explained in more detail below, that the esters can be prepared by methods other than esterifying the acid with the alcohol and, in practice, often are.

So far as the various values of R² and R³ are concerned, it is preferred that when these groups include alkyl, or carbo-alkoxy groups, the groups contain up to 6 carbon atoms, and, more particularly, up to 3 carbon atoms, methyl, ethyl, propyl, carbo-methoxy, carbo-ethoxy, and carbo-propoxy, being of particular interest. When R² and/or R³ represents a halogeno group, it is preferably fluorine, chlorine or bromine. When R² and R³ each represent halogeno they are preferably, but not necessarily the same halogen.

The esters of the present invention fall into various sub-classes structurally, depending primarily upon the nature of substituent R² and R³. One sub-class of particular interest are those compounds where R¹ and R³ each represent hydrogen and R² represents an alkyl group of at least two carbon atoms. We have now found that in this sub-class the highest toxicity to houseflies and mustard beetles of 5-benzyl-3-furylmethyl esters of 3-β-alkylvinyl-2,2-dimethylcyclopropane carboxylic acid is shown when the alkyl group is ethyl.

Further sub-classes of particular interest are those esters where R¹ and R³ each are hydrogen and R² is chlorine or bromine and those compounds where R¹ is methyl and R³ is hydrogen, and R² is hydrogen or an alkyl group containing up to 6 carbon atoms such as methyl, ethyl or propyl.

Another sub-class of particular interest are those compounds where R² represents hydrogen and R³ represents a carboalkoxy group. These esters are esters of a demethyl pyrethric acid analogue which is devoid of the methyl substituent on the β-carbon atom of the 3-substituent. A further sub-class of considerable importance are those esters where R² represents methyl and R³ represents a carboalkoxy group, where the alkoxy residue contains at least two carbon atoms. These esters are esters of pyrethric acid analogues which do not contain the carbomethoxy substituent on the β carbon atom of the 3-substituent.

Further sub-classes of particular interest are those esters where R² represents an alkyl group of at least two carbon atoms; again these esters are esters of a pyrethric acid homologue which does not contain the methyl substituent on the asterisked carbon atom of formula I. In these esters, R³ may represent the carbomethoxy group (which is present in pyrethric acid) or a higher homologue thereof.

A useful group of active insecticidal esters of the invention are those where R¹ represents hydrogen and R² and R³ each represents a halogeno group. Certain esters of the 3-dihalovinyl acids are also of particular value because of their greater light stability than the corresponding chrysanthemates. These are therefore suitable for use against pests of agricultural crops in sunlight, as well as in domestic and horticultural situations.

A further halogenated sub-class of interest are those esters where R¹ represents hydrogen, R² represents halogeno and R³ represents carboalkoxy. The acid residues in these esters are analogues of pyrethric acid where the methyl substituent on the β-carbon atom of the 3-substituent is replaced by halogeno and homologues of these acids where the carbomethoxy group is replaced by a carboalkoxy group containing at least 3 carbon atoms. The halogen is preferably chlorine or bromine and the carboalkoxy group is preferably carbo-methoxy, -ethoxy or -n-propoxy.

Preferred esters of the present invention include those which are structurally esters of a 2,2-dimethyl-3-substituted cyclopropane carboxylic acid where the 3-substituent is: ##STR5##

When the esters of the present invention are alkyl esters, it is preferred that the alkyl group be one containing up to 6 carbon atoms and we have found that methyl, ethyl and tertiary butyl esters are amongst those which can be readily prepared by our synthetic methods.

When the ester is one structurally derived from a furylmethyl alcohol it is preferred that the furylmethyl alcohol be one of the 3-furylmethyl alcohols described in British Patent Specification No. 1,168,798. In the furylmethyl alcohols, and particularly in the 3-furylmethyl alcohols, it is preferred that R⁷ and R⁸ each represent hydrogen or groups containing up to 4 carbon atoms, particularly a methyl group and that Y represents a phenyl group which is unsubstituted or substituted in the ring by a group containing up to 4 carbon atoms, e.g. methyl or methoxy, or by chlorine, and Z═CH₂, and D═H. Analogues of these compounds where Z═O, S or CO and D═CN or C.tbd.CH can also be used. Other compounds of interest are those where Y represents a hydrogen atom, an alkyl group containing up to 4 carbon atoms, an alkenyl group containing up to 4 carbon atoms, e.g. vinyl, an alkadienyl group containing up to 4 carbon atoms or an alkynyl group e.g. propargyl or a furyl group.

Specific alcohols of this category, from which the esters of the invention are structurally derivable, include 5-benzyl-3-furylmethyl alcohol, 5-benzyl-2-methyl-3-furylmethyl alcohol, 5-benzylfurfuryl alcohol, 4-benzyl-5-methyl-furfuryl alcohol, 5-p-xylyl-furfuryl alcohol, 2,4,5-trimethyl-3-furylmethyl alcohol, 4,5-dimethylfurfuryl alcohol, 5-phenoxy- and 5-benzoyl-3-furylmethyl alcohol and α-cyano- and α-ethynyl- -5-benzyl-, -5-benzoyl- and -5-phenoxy-3-furylmethyl alcohol.

The cyclopentenolones from which the esters of the invention are structurally derivable are those unsubstituted in the 3-position or those substituted in the 3-position by a methyl group, (R⁹ =H or CH₃).

The cyclopentenolones unsubstituted in the 3-position are described in British Patent Specification No. 1,305,025. Some of these alcohols are the 3-demethyl analogues of the alcohols from which the naturally occurring pyrethrins are derived. In the present invention, it is preferred that R¹⁰ and R¹¹ each represent hydrogen, methyl or ethyl and R¹² represents an aryl group such as a phenyl group or a phenyl group substituted by a halogeno or alkyl or alkoxy substituent, of 1 to 4 carbon atoms, for example tolyl, xylyl, p-chlorophenyl or p-methoxyphenyl, R¹² may also represent a 2- or 3-furyl group or an alkenyl group such as a vinyl, prop-1-enyl or buta-1,3-dienyl group.

When the esters of the invention are structurally derivable from the cyclopentenolones which are substituted in the 3-position by the methyl group, (R⁹ =methyl), the esters may be derived from allethrolone (R¹⁰ =R¹¹ =H, R¹² =vinyl), pyrethrolone (R¹⁰ =R¹¹ =H, R¹² =buta-1,3-dienyl), cinerolone (R¹⁰ =R¹¹ =H, R¹² =prop-1-enyl), jasmolone (R¹⁰ =R¹¹ =H, R¹² =but-1-enyl) or furethrolone (R¹⁰ =R¹¹ =H, R¹² =2-furyl).

When the esters of the invention are phthalimidomethyl esters where R is of formula V, they may be phthalimido, dihydrophthalimido or tetrahydrophthalimido-methyl esters where the phthalimido, dihydrophthalimido or tetrahydrophthalimido residue is one described in British Patent Specification Nos. 985,006, 1,052,119 or 1,058,309. 3,4,5,6-Tetrahydrophthalimido-methyl esters are of particular interest.

When the esters of the invention are those where R is of formula VI, it is preferred that they be 3-benzylbenzyl esters, 3-benzoylbenzyl esters or 3-phenoxybenzyl esters although each of the rings may be substituted by up to 3 chloro and/or methyl groups. Other esters of particular interest where R is of formula VI are those where Z³ represents O or CH₂ and D represents --CN or --C.tbd.CH, e.g. esters of α-cyano- or α-ethynyl-3-phenoxybenzyl alcohol and of α-cyano- or α-ethynyl-3-benzylbenzyl alcohol and esters of α-cyano- or α-ethynyl- -3-benzoylbenzyl alcohol.

The compounds of the present invention exhibit geometrical and optical isomerism and consequently may be prepared in optically active forms which may subsequently be mixed together or as racemic mixtures which may subsequently be resolved into optically active forms. In addition, optically active forms or racemic mixtures can be separated into the individual diastereoisomers. In addition to the geometrical isomerism that results from the configuration of the substituents on the cyclopropane ring with respect to one another and the ring, there is also the possibility of geometrical isomerism in the side chain on position 3 when R¹, R² and R³ are such that the unsaturated side-chain is unsymmetrically substituted. In the α-cyano- and α-ethynyl compounds (D═CN or C.tbd.CH), there is a further possibility of optical isomerism and the compounds envisaged include esters of both the racemic mixture and of the separate isomers resulting from the asymmetry at the carbon atom bearing the D group. The various optical and geometrical isomers of the esters of the invention usually have different insecticidal toxicities and knock-down potency.

The compounds of formula II can exist in the form of geometrical isomers depending upon whether the hydrogen atoms carried at C₁ and C₃ of the cyclopropane ring are in the cis or trans relationship. Because of the unsymmetrical substitution at C₁ and C₃ on the cyclopropane ring, each cis isomer can exist in one of two optically active forms and each trans isomer can exist in one of two optically active forms. When the absolute configuration at C₁ of compounds of formula II is the same as that at C₁ in (+)-trans chrysanthemic acid, the absolute configuration of C₁ in compound II is designated 1R. The absolute configuration of C₃ in compounds of formula II cannot vary independently of the C₁ configuration in a compound having specified geometrical configuration and, for a dihalo compound having trans configuration and R configuration at C₁, strict application of the sequence rule (Cahn, R. S. Ingold C. and Prelog V. Angew. Chem. Int. Ed. 5, 385 (1966)) requires the designation S to be applied at C₃. However, application of the same sequence rule to the same C₃ centre in (+)-trans chrysanthemic acid requires that centre to be designated R, even though it is directly related in absolute configuration to the configuration designated S in dihalo compounds of formula II. This is because the nature of the substitution at C₃ is different in (+)-trans chrysanthemic acid from that of dihalo compounds of formula II. However, because the specification of the geometrical configuration and the absolute configuration at C₁ fixes the C₃ configuration absolutely, and to avoid possible confusion arising from the fact that different compounds of the same series may otherwise require sometimes R, sometimes S designations of the configuration at C₃, we have proposed the nomenclature (1R)-trans for such compounds as this provides sufficient information to determine the absolute configuration of the cyclopropane ring part of the molecule.

Similar considerations have resulted in our designating compounds having the same absolute configuration as (+)-cis chrysanthemic acid as (1R)-cis compounds. In cases where we have dealt with compounds having the same configuration as (-)-trans or (-)-cis chrysanthemic acid, we are applying the designations (1S)-trans and (1S)-cis respectively.

Apart from the (1R)-cis, (1R)-trans, (1S)-cis and (1S)-trans compounds, esters derived from (±)-trans and (±)-cis acids (now designated (1RS)-trans and (1RS)-cis respectively) are also of interest, as well as mixtures of (1R)-trans and (1R)-cis and (1RS)-trans and (1RS)-cis with varying proportions of the cis and trans isomers.

There is as mentioned above a further possible site of asymmetry in compounds of formula II, that is when the R group is of formula III or VI and substituent D on the α-carbon is other than hydrogen. These compounds of formula II can exist in forms having the absolute (R)-configuration or in forms having the absolute (S)-configuration at this α-carbon atom.

When R¹ represents hydrogen and R² and R³ each represent bromine, then an unexpected level of selectivity in combatting certain pests is obtained with those compounds where the configuration about the cyclopropane ring is cis and R represents α-cyano-3-benzoylbenzyl. This unexpected selectivity exists in relation to the control of certain lepidopterous pests Ephestia kuhniella which is a stored product pest. The Ephestia frequently carry a hymenopterous parasite called Venturia canescens. An ideal agent to control the lepidopterous stored products pest should exhibit selectivity towards killing the lepidopterous pest over killing the Venturia parasite. If such a selective control agent were to be used, which were to kill the lepidopterous pest but leave the parasite unaffected, then in the event of a subsequent infestation of the stored product by further lepidopterous pest, the Venturia remaining from the previous infestation would be able to prevent the development of the subsequent infestation of lepidopterous pests and so prolong the period during which the stored product could be kept free of infestation on the basis of a single treatment with the control agent. It has been found that the types of compound identified above to exhibit such selectivity. A particularly valuable selectivity is observed in compounds of this type when the ester is in the form of a substantially pure optical isomer with respect to the cyclopropane ring and the ester has (R)-configuration at C₁ of the cyclopropane ring as is illustrated in Example 40.

The insecticidal esters of the present invention may be prepared by esterification involving the reaction of an alcohol or derivative thereof of formula R-Q e.g. of formula VII, VIII or VIIIA, and a cyclopropane carboxylic acid or derivative thereof of formula IX, ##STR6## where Q and COQ¹ are functional groups or atoms which will react together to form an ester linkage and R, R¹, R², R³, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹² and D, Z, Z¹, Z², Z³, Y and n are as defined above.

It is usually convenient in practice either to react the acid or acid halide with the alcohol (COQ¹ =COOH or CO-halide and Q=OH) or to react a halogeno compound (Q=halogen) with a salt of the carboxylic acid (COQ¹ =COO.sup.⊖ M.sup.⊕ where M is, for example, a silver or triethylammonium cation).

For reasons which will shortly be described, reactant IX normally becomes available initially in the form of a lower alkyl ester, (COQ¹ =COO alkyl) where the alkyl group contains 1 to 6 carbon atoms and consequently, a particularly convenient way of preparing the insecticidal esters of the invention, except where R³ is carboalkoxy, is to subject the alkyl ester of formula IX to transesterification using an alcohol ROH, e.g. in the presence of a basic catalyst. When the alkyl ester contains a base sensitive group, e.g. R³ =carboalkoxy, base catalysed transesterification is undesirable and can be avoided by preparing a t.-butyl ester which can be converted into the free acid by acid catalysed decomposition and the free carboxylic group esterified directly or via a salt or halide.

The esters of the present invention can also be prepared by reaction between a phosphorane or ylide of formula X and an ester of 2,2-dimethyl cyclopropane carboxylic acid substituted at the 3-position by an acetyl group or an aldehyde group of formula XI: ##STR7##

In formulae X and XI R¹, R², R³ are as defined above and R is a group as defined above which will not interfere in the Wittig reaction and Z⁴ ; which in principle can represent any organic radical, will normally be a phenyl radical since the stability of the trisubstituted phosphorus oxide which is formed as the by-product in the reaction is particularly high and this favours completion of the reaction between the phosphorane X and the aldehyde or ketone XI. Alternatively, the phosphorane X can be replaced by another equivalent Wittig reagent or other ylide.

Esters of the present invention where R¹ represents hydrogen can be prepared by reaction with an aldehyde of formula XI while esters of the invention where R¹ represents methyl can be prepared by reaction of a 3-acetyl compound of formula XI. The phosphorane X and aldehyde or ketone XI are preferably reacted in substantially equimolar proportions, conveniently in the solvent in which the phosphorane itself has been prepared. As will be discussed in more detail below, this may be an aromatic hydrocarbon such as benzene or a polar solvent such as dimethyl sulphoxide or a chlorinated hydrocarbon such as dichloromethane. The product can be improved if reaction is carried out in an inert atmosphere e.g. under nitrogen. The reaction between the phosphorane and aldehyde or ketone is normally quite rapid and the desired ester can be recovered from the reaction mixture after a reaction time of less than 1 hour although reaction times of up to 24 hours have been used. The desired ester can be recovered from the reaction product by solvent extraction e.g. with diethyl ether or petroleum ether.

The phosphorane of formula X where neither R² nor R³ represent halogen can be prepared from the corresponding phosphonium salt which in turn can be prepared by reacting the appropriately substituted methyl halide with a triorganophosphine in accordance with the following reaction scheme: ##STR8##

The flexibility of the present synthetic method results from the fact that the initial starting material is the substituted methyl halide R³ (R²)CH hal and the availability of whole series of such substituted halides permits the production of whole series of 2,2-dimethyl cyclopropane carboxylic acids which are substituted in the 3-position by various groups which have previously been difficult or impossible to prepare. In the above-mentioned synthesis of the phosphorane, it is convenient to start with a substituted methyl bromide which is reacted with triphenylphosphine to give the corresponding triphenylphosphonium bromide and subsequently converting the phosphonium salt to the phosphorane or ylide which can be designated by the formula given above. The conversion of the phosphonium salt to the phosphorane can be brought about by treating the phosphonium salt with an alkali metal amide or alkali metal methyl sulphinyl methide (.sup.⊖ CH₂.SO.CH₃ M.sup.⊕). For example, sodamide can be prepared by reacting sodium in liquid ammonia and the reaction carried out in the presence of the excess ammonia as the liquid medium. At the end of the reaction, the liquid ammonia can be allowed to evaporate and the phosphorane taken up into an organic solvent such as benzene and the subsequent reaction with aldehyde or ketone XI carried out in this organic solvent. Alternatively, dimethyl sulphoxide can be reacted with sodium hydride to give sodium methyl sulphinyl methide and the production of the phosphonium salt carried out using this reagent and, following formation of the phosphorane, the subsequent reaction with the aldehyde or ketone XI can be carried out in the same reaction medium.

When R³ =carboalkoxy, the conversion of the phosphonium salt to the phosphorane can be brought about by treating the phosphonium salt with an alkali metal amide in liquid ammonia or in aqueous alkali metal hydroxide solution, e.g. 5% NaOH. The liberated phosphorane can be filtered from the solution and subsequently reacted with the aldehyde XI in a suitable solvent e.g. CH₂ Cl₂.

Phosphoranes where R³ represents carboalkoxy and R² represents hydrogen or methyl can be prepared by the above described procedures using a haloacetate or α-halopropionate alkyl ester as the substituted methyl halide but this synthesis is not entirely satisfactory for the preparation of phosphoranes of this type where R² represents an alkyl group of 2 or more carbon atoms. For such higher homologues, a phosphorane where R³ represents hydrogen and R² represents the desired alkyl group is first prepared as an intermediate by the procedures described above starting from an alkyl halide of at least 3 carbon atoms and this intermediate phosphorane is then reacted with the appropriate alkyl chloroformate ester to introduce the desired carboalkoxy group.

Phosphoranes where R² and/or R³ represent halogen can be prepared by simple modifications of the above described synthesis.

When R² and R³ each represent halogen, a carbon tetrahalide can be used in place of the substituted methyl halide and the reaction proceeds in accordance with the equation: ##STR9## the dehydrohalogenation of the quaternary phosphonium halide proceeding spontaneously.

Halogenated phosphoranes can also be prepared by halogenating an unhalogenated phosphorane, itself obtained by the above described procedures in accordance with the following reaction scheme: ##STR10## where hal=halogen, R³ =halogen and R² is as defined above.

We have found that it is desirable that the carboxyl group in the aldehyde or ketone reactant XI be esterified as a lower alkyl ester in order to achieve the most satisfactory results in the reaction with the phosphorane X. This means that the alkyl esters of the present invention are produced directly and, since it is possible to convert these alkyl esters into the insecticidal esters of the invention, except those containing a base sensitive group, e.g. R³ =carboalkoxy, by a simple base catalysed transesterification reaction, it is not necessary to convert the alkyl esters of the invention into the corresponding acid in order to produce the insecticidal esters. However, indirect conversion of the alkyl esters to the insecticidal esters is possible in accordance with the present invention and, when operating in accordance with this embodiment, the carboalkoxy group in the ester of formula II can be converted by conventional hydrolysis into the corresponding free carboxylic acid group going, via the alkali metal or other salt for instance, and this carboxylic acid can be directly esterified as described above or alternatively can be converted first into an acid halide e.g. the chloride and this acid halide converted into an ester by reaction with an appropriate alcohol of formula ROH as described above.

In the case where R is a t.-butyl group, the alkyl ester can be converted into the free acid by heating with a small amount of toluene-4-sulphonic acid. This reaction can be carried out in benzene and the resulting carboxylic acid converted to the acid chloride in the benzene solution without isolation.

In the synthetic methods described so far, alkyl esters of the invention are prepared by a Wittig reaction between a phosphorane X and an alkyl ester of a carbonyl compound XI and the resulting alkyl ester of the invention converted to an insecticidal ester by transesterification or via the force acid and acid chloride which is subsequently reesterified e.g. with 5-benzyl-3-furylmethyl alcohol. It is usually most convenient to operate in this manner but is not essential to do so and a practical alternative is to produce the insecticidal ester directly by reacting the phosphorane X with a carbonyl compound of formula XI where R represents a group of formula III, IV, V, VI, VIA or VIB as defined above.

Such carbonyl compounds of formula XI may be prepared by the synthetic methods described above but converting the group R from an alkyl group to a group of formula III, IV, V, VI, VIA or VIB before the Wittig reaction instead of after the Wittig reaction as described above.

Carbonyl compounds of formula IX can be prepared by ozonolysis of the corresponding ester of chrysanthemic acid, when oxygenation of the double bond in the isobutenyl side chain occurs. Thus, provided R does not contain a group degradable under ozonolysis conditions, the required carbonyl compound XI for this alternative method can be obtained directly by ozonolysis of the chrysanthemate and the ozonolysed chrysanthemate XI used in the Wittig reaction to give the insecticidal ester. Some furan containing compounds are degraded under ozonolysis conditions so the 5-benzyl-3-furylmethyl ester of caronaldehyde cannot be obtained by direct ozonolysis of the corresponding chrysanthemate (it must be obtained in two stages via an alkyl ester of caronaldehyde) but a 3-phenoxybenzyl ester can be so treated.

Acids of the general formula IX (COQ¹ =COOH) where R¹ =R³ =H and R² =an alkyl group containing at least two carbon atoms can be prepared by reaction between 2-ethynyl-3,3-dimethyl cyclopropane carboxylic acid and an appropriate alkyl halide in the presence of an alkali metal followed by catalytic semi-hydrogenation. Acids where R² =R³ =Cl can be prepared by reacting ethyl diazoacetate with 1,1-dichloro-4-methyl-penta-1,3-diene and converting the ethyl ester to the acid.

Alcohols and halides of formula VIII are described in British Patent Specification No. 1,305,025.

Alcohols of formula VII or VIIIA where D represents CN or C.tbd.CH can be prepared by conventional methods from the corresponding aldehydes. Thus, a furaldehyde or benzaldehyde can be reacted with (a) HCN, conveniently generated in situ from KCN and acid, when addition of HCN occurs forming the cyanhydrin or (b) an alkali metal acetylide in liquid ammonia.

Alcohols of formula ROH where R is a group of formula VI where D represents hydrogen may be prepared by reduction of the corresponding acids or esters e.g. with a hydride, or by conversion of the corresponding halide to an ester e.g. by reaction with sodium acetate, followed by hydrolysis of the ester, or by reaction of formaldehyde with a Grignard reagent derived from the corresponding halide. The halides of formula R-halogen where R is a group of formula VI where D represents hydrogen can be prepared by halomethylation of the compound: ##STR11## or side chain halogenation of: ##STR12##

The benzoylbenzyl alcohols and derivatives thereof may be prepared from 3-methyl-benzophenone. The benzophenone is first brominated in the side chain using N-bromosuccinimide. This bromination gives a mixture of compounds which are monobrominated and dibrominated in the methyl side chain. This mixture of monobromo and dibromo compounds may then be hydrolysed, under acid or alkaline conditions, e.g. by refluxing with alcoholic KOH, when the monobromo methylbenzophenone is converted directly into the desired 3-benzoylbenzyl alcohol while the dibromo methyl compound is converted into 3-benzoylbenzaldehyde which may be separated from the alcohol by fractionation. The benzaldehyde may then be reacted with HCN under the conventional conditions for this reaction when the aldehyde is converted into α-cyano-3-benzoylbenzyl alcohol. This last-mentioned reaction produces the α-cyano compound as a racemic mixture.

Normally, the primary or secondary alcohol prepared by the syntheses described above is used directly in the esterification with the cyclopropane-carboxylic acid to produce esters of the invention. However, if it is desired to use another esterification technique, the primary or secondary alcohol may be converted into another esterifiable derivative by methods known per se.

It is also possible to produce individual isomers of the present invention by first preparing isomer mixtures of the present invention by the esterification techniques described above and then subjecting the isomer mixture to thin layer chromatography or to high pressure liquid chromatography which enables the individual isomers to be eluted sequentially from, for example, silica gels, using solvent mixtures such as hexane/diethyl ether.

One or more of the insecticidal esters of the invention may be formulated with an inert carrier or diluent to give insecticidal compositions and these may be prepared, for example, in the form of dusts and granular solids, wettable powders, mosquito coils and other solid preparations or as emulsions, emulsifiable concentrates, sprays and aerosols and other liquid preparations after the addition of the appropriate solvents, diluents and surface active agents. The compositions usually contain 0.0001 to 95% by weight, preferably up to 50% by weight of the active compound.

Pyrethrum synergists such as piperonyl butoxide, Sesamex or tropital, may be added to these compositions. Certain insecticidal esters of the invention show significant superiority over structurally similar esters e.g. chrysanthemates or pyrethrates, in the ability to respond to synergists and many esters of the invention have a synergistic factor several times greater than those exhibited by other synthetic esters. Many of the esters derived from acids of the present invention are much more stable to light than those of previously known acids, and dihalovinyl esters are especially favored in this connection.

The insecticidal compositions may also include known synthetic pyrethrins to improve kill and/or knockdown or to synergise the activity of the known pyrethrin and/or that of the synthetic pyrethrins of the invention.

The new esters of the invention or insecticidal compositions containing them may be used for killing insects or controlling the level of insects on a domestic or agricultural scale by treating the insects themselves or an environment susceptible to insect attack with the compounds or compositions. The compounds of the invention also exhibit valuable acaricidal properties, particularly against cattle tick.

The following Examples are given to illustrate the present invention (temperatures are in °C., refractive indices are measured at 20° C. Unless otherwise indicated, the hydrogen atoms at C₁ and C₃ of the cyclopropane ring are in the trans-relationship to one another).

EXAMPLE 1

n-Pentyl triphenylphosphonium iodide (9.5 g., 0.02M), prepared by reaction of n-pentyl iodide with triphenylphosphine, was added slowly, under nitrogen, to sodamide [0.7 g. sodium (0.03M) in liquid ammonia (130 ml.)]. The mixture was stirred for 0.5 hours and the ammonia allowed to evaporate (2 hours). Benzene (130 ml.) was added and the mixture refluxed, under nitrogen, for 0.5 hours, allowed to cool and the supernatant liquid containing the phosphorane decanted off under nitrogen.

The phosphorane solution was added dropwise, under nitrogen, to a stirred solution of methyl (1R)trans caronaldehyde (1.0 g., 0.0064M) (from ozonolysis of methyl ester of (1R)-trans-chrysanthemic acid) in dry benzene (15 ml.). The addition was completed in 10 minutes and the solution was stirred for a further 0.5 hours. The solution was evaporated, the residue dissolved in diethyl ether, the organic solution washed with water and dried. Evaporation yielded a colourless mixture which was further extracted with petroleum ether (60°-80°), evaporation of which yielded a colourless liquid b.p. 107°-109°/5 mm., yield (1.07 g., (80%), n_(D) 1.4622) which was identified by NMR spectroscopy as 2,2-dimethyl-3-(hex-1-enyl)-cyclopropane carboxylic acid methyl ester. (Compound C').

EXAMPLE 2

The procedure described in Example 1 was repeated replacing the n-pentyl iodide with equivalent amounts of n-propyl iodide or n-butyl bromide, to give alkyl esters of the invention of formula II and of refractive index as indicated below:

    ______________________________________                                         Compound   R.sup.2  R.sup.3                                                                              R.sup.1                                                                               R    n.sub.D                                  ______________________________________                                         A'         C.sub.2 H.sub.5                                                                         H     H      CH.sub.3                                                                            1.4581                                   B'         n-C.sub.3 H.sub.7                                                                       H     H      CH.sub.3                                                                            1.4572                                   ______________________________________                                    

In Compound A', the 3-but-1-enyl substituent is in the trans relationship to the cyclopropane ring. Its (1R)-cis-isomer (in free acid form) was made by the following procedure. (In both Compound A' and its cis isomer, the configuration around the ethylenic double bond in the 3-substituent is cis.)

n-Propylidene phosphorane [prepared by reacting the corresponding phosphonium iodide (7 g.) with sodamide, (sodium (0.7 g.)/liquid ammonia (150 ml.))] in dry benzene (100 ml.) was added dropwise, with stirring, to a solution of the internal hemi-acetal of cis-3-formyl-2,2-dimethyl-cyclopropane carboxylic acid (0.7 g.) (French Patent Specification No. 1,580,475) in benzene (10 ml.), under nitrogen. The benzene was evaporated off and the residue dissolved in methylene chloride (75 ml.) and washed with water and sodium carbonate solution. Acidification of the carbonate extract yielded an acid which was extracted with methylene chloride, dried (Na₂ SO₄), and evaporated to give (1R)-cis-3-but-1-ene-2,2-dimethyl-cyclopropane carboxylic acid (0.7 g.). (Compound A' cis).

EXAMPLE 3

The procedure described in Example 1 was repeated replacing the methyl trans-carbonaldehyde by an equivalent weight of ethyl (1RS)-cis-trans-3-acetyl-2,2-dimethylcyclopropane carboxylate and replacing the n-pentyl iodide by methyl iodide, ethyl iodide, n-propyl iodide, or n-butyl bromide to give the alkyl esters of formula II as indicated below having the following refractive index:

    ______________________________________                                         Compound  R.sup.2    R.sup.3                                                                              R.sup.1                                                                               R    n.sub.D                                 ______________________________________                                         F'        H          H     CH.sub.3                                                                              C.sub.2 H.sub.5                                                                     1.4469                                  G'        (1) CH.sub.3                                                                              H     CH.sub.3                                                                              C.sub.2 H.sub.5                                                                     1.4570                                  H'        (2) C.sub.2 H.sub.5                                                                       H     CH.sub.3                                                                              C.sub.2 H.sub.5                                                                     1.4570                                  I'        n-C.sub.3 H.sub.7                                                                         H     CH.sub.3                                                                              C.sub.2 H.sub.5                                                                     1.4573                                  ______________________________________                                          (1) (2) the stereochemistry of these esters about the double bond              αβ to the cyclopropane ring is .sup.(1) 40:60 and .sup.(2)          80:20 Z:E.                                                               

EXAMPLE 4

A suspension of sodium hydride in oil (0.50 g., approx. 0.0095M NaH) was washed with dry diethyl ether (20 ml.) under nitrogen. Dry dimethylsulphoxide (DMSO) (3.5 ml.) was added and the mixture heated to 80° for 0.5 hours. After cooling, a slurry of n-butyl triphenylphosphonium bromide (3.80 g., 0.0104M) (prepared by reaction of n-butyl bromide with triphenylphosphine) in DMSO (9 ml.) was added with stirring, the remainder of the slurry being washed in with diethyl ether (10 ml.). The mixture was stirred for 0.5 hours and ethyl 3-acetyl-2,2-dimethyl cyclopropane carboxylate (1.0 g., 0.0054M) was added. The mixture was thoroughly shaken and stirred for 24 hours under nitrogen. Ice was added and the mixture acidified with aqueous potassium hydrogen sulphate. After diethyl ether extraction, the organic solution was washed with water, saturated sodium chloride solution, and evaporation of the dried solution (Na₂ SO₄) yielded a solid which on extraction with petroleum spirit (60°-80°) and evaporation yielded a colourless liquid b.p. 112°-188°/20 mm, 0.52 g, (43%) n_(D) 1.4573. This liquid was identified by NMR spectroscopy as the compound of formula II where R² =n-C₃ H₇, R³ =H, R¹ =CH₃ and R=C₂ H₅. (Compound I').

EXAMPLE 5

Chloromethylenetriphenylphosphonium chloride (2.1 g, 0.006M) and dry piperidine (0.51 g, 0.006M), in dry diethyl ether (15 ml) was treated, under nitrogen, with 8% n-butyl lithium in hexane (4.8 ml, [0.388 g, 0.006M]). The mixture was stirred at room temperature for 1.5 hours and t.-butyl (1R)-trans-caronaldehyde (1.27 g, 0.0064M) in dry benzene (5 ml) was added. The mixture was left to stir for 3 days and the solution filtered and the residue washed with dry diethyl ether. The filtrate was washed with 10% H₂ SO₄, water and evaporation of the dried (Na₂ SO₄) solvent followed by distillation yielded a colourless liquid b.p. 100°/20 mm. (70%). This was identified by NMR spectroscopy as the ester of formula II where R³ =Cl, R² =H, R¹ =H and R=t.-C₄ H₉ and was found to have n_(D) 1.4670. The stereochemistry about the double bond αβ to the ring was 20:80 Z:E.

The alkyl esters whose preparation is described above in Examples 1 to 5 were then converted into the corresponding 5-benzyl-3-furylmethyl ester by the procedures described below in Examples 6-9.

EXAMPLES 6-7

0.2 mols of sodium were slowly added to a solution of 2 mols of 5-benzyl-3-furylmethyl alcohol in toluene. When the reaction between the sodium and the alcohol to give the sodium alcoholate was complete, a solution containing about 1 molar proportion of the alkyl ester of formula II in toluene was added and the mixture heated under reflux with separation of the methanol or ethanol evolved in the trans-esterification reaction. After the solution had cooled, the desired 5-benzyl-3-furylmethyl ester was recovered in yields of 50-70%, based on the weight of alkyl ester, by chromatography on alumina. The structure of the esters as being in accordance with formula II was confirmed by NMR spectroscopy and gas/liquid chromatography.

The following insecticidal esters were prepared:

    ______________________________________                                         Compound                                                                               R.sup.3  R.sup.2                                                                              R.sup.1 n.sub.D                                         ______________________________________                                         A       C.sub.2 H.sub.5                                                                         H     H       1.5174 (trans isomer)                             A cis C.sub.2 H.sub.5                                                                         H     H       1.5347 ((1R) cis isomer)                        B       n-C.sub.3 H.sub.7                                                                       H     H       1.5177                                          C       n-C.sub.4 H.sub.9                                                                       H     H       1.5128                                          F       H        H     CH.sub.3 *                                                                             1.5157                                          G       CH.sub.3 H     CH.sub.3 *                                                                             1.5206                                          H       C.sub.2 H.sub.5                                                                         H     CH.sub.3 *                                                                             1.5180                                          I       n-C.sub.3 H.sub.7                                                                       H     CH.sub.3 *                                                                             1.5118                                          ______________________________________                                          Compounds A-I are all compounds of formula II where R =                        5benzyl-3-furylmethyl.                                                         *These compounds are a mixture of (1RS)cis-trans-isomers.                

Compound A cis was prepared from A' cis by treating with thionyl chloride in benzene to convert A' cis to the acid chloride and then reacting the acid chloride with 5-benzyl-3-furylmethyl alcohol in benzene in the presence of pyridine.

EXAMPLE 8

Methyl 2,2-dimethyl-3-(but-1-enyl)-cyclopropane carboxylate, (prepared as described in Example 2), (2.8 g.) was refluxed for 1 hour with 1.8 g. NaOH in 70 mls. methanol. The reaction mixture was then diluted with water, acidified and extracted with diethyl ether to give 2.01 g. 2,2-dimethyl-3-(but-1-enyl)-cyclopropane carboxylic acid, n_(D) 1.4719. The acid was then converted into its acid chloride by reaction with thionyl chloride and the acid chloride then esterified by reaction in benzene with an equimolar amount of (±)-allethrolome (+)-pyrethrolone, 3-benzylbenzyl alcohol or 3-phenoxybenzyl alcohol in the presence of an equimolar amount of pyridine. The reaction mixture was then chromatographed on neutral alumina and the solvent evaporated to give the desired ester. The following insecticidal esters were prepared:

    ______________________________________                                         Compound                                                                               R.sup.2  R.sup.3                                                                              R.sup.1                                                                              R           n.sub.D                               ______________________________________                                         Q       C.sub.2 H.sub.5                                                                         H     H     (±)-allethronyl                                                                         1.5009                                R       C.sub.2 H.sub.5                                                                         H     H     (+)-pyrethronyl                                                                            1.5159                                S       C.sub.2 H.sub.5                                                                         H     H     3-benzylbenzyl                                                                             1.5488                                T       C.sub.2 H.sub.5                                                                         H     H     3-phenoxybenzyl                                                                            1.5439.                               ______________________________________                                    

EXAMPLE 9

A mixture of the tertiary butyl ester described in Example 6 (410 mg.) toluene-4-sulphonic acid (47.5 mg.) and dry benzene (15 ml.) were refluxed 2 hours and cooled to give a solution of the corresponding carboxylic acid. Pyridine (163 mg.) and thionyl chloride (213 mg.) were then added, and the mixture allowed to stand for 2 hours to give the acid chloride. A mixture of substantially equimolar proportions of the acid chloride, 5-benzyl-3-furylmethyl alcohol and pyridine was prepared in dry benzene and the mixture cooled and allowed to stand at room temperature overnight. The mixture was then poured through a column of neutral alumina and eluted with benzene to give a compound of formula II where R³ =Cl, R² =H, R¹ =H and R=5-benzyl-3-furylmethyl. This ester, designated ester K, has n_(D) 1.5418.

EXAMPLE 10

Triphenyl phosphine (13 g.) was dissolved in dry benzene (60 ml.) and ethyl bromoacetate (8.3 g.) was added dropwise. The solution was heated at 70° for 2 days, and then cooled and filtered. The residue was washed with benzene and dried to give about 16 g. of (ethoxycarbonylmethyl) triphenylphosphonium bromide. The phosphonium salt (10 g.) was dissolved in water (250 ml.) and 5% aqueous sodium hydroxide was added dropwise with stirring until the solution became alkaline to litmus. The resulting precipitate was filtered off, washed with water and dried. Crystallisation from ethyl acetate/petroleum spirit gave (ethoxycarbonyl methylene) triphenyl phosphorane as a colourless solid in about 80% yield.

The phosphorane (3.2 g., 0.0092M) in dry dichloromethane (30 ml.) was added to t.-butyl(1R)trans-caronaldehyde (1.5 g., 0.0076M) (from ozonolysis of t.-butyl (+)-trans-chrysanthemic acid) in dichloromethane (30 ml.) with stirring under nitrogen; stirring was continued at room temperature for 2.5 days. The solution was evaporated, and the residue extracted with petroleum spirit (60°-80°) which on evaporation and distillation yielded a colourless liquid b.p. 112°/0.7 mm., 1.60 g. (79%) n_(D) 1.4666 which was identified by NMR spectroscopy and gas/liquid chromatography as a compound of formula II where R³ =carboethoxy, R² =H and R=t.-butyl. (Compound P19/B').

EXAMPLE 11

The procedure described in Example 10 was repeated but replacing the bromoacetic acid ethyl ester by an equivalent weight of bromoacetic acid methyl ester and by bromoacetic acid propyl ester and making any necessary variations in reaction time or temperature during phosphorane formation, to give compounds of formula II where R² =H, R=t.-butyl and R³ =carbomethoxy or carbo-n-propoxy, n_(D) 1.4677 and 1.4723, (compounds P19/A' and P19/C') respectively.

EXAMPLE 12

The procedure described in Example 10 was repeated replacing the bromoacetic acid ethyl ester by an equivalent weight of α-bromopropionic acid ethyl ester and propyl ester. Esters of formula II were obtained where R² =methyl, R=t.-butyl and R³ =carboethoxy and carbo-n-propoxy, n_(D) 1.4658 and 1.4712 (Compounds P19/D' and P19/E') respectively.

EXAMPLE 13

n-Propyl triphenyl phosphonium iodide was prepared by the procedure described in Example 10 replacing the ethyl bromoacetate by n-propyl iodide. The phosphonium iodide (9.5 g.) was then treated under nitrogen with the NaNH₂, obtained from 0.5 g. Na in 100 mls. liquid NH₃ and the NH₃ allowed to evaporate over 2 hours. Benzene (120 mls.) was then added, the mixture refluxed for 15 minutes and 1.08 g. methyl chloroformate in 50 mls dry benzene then added dropwise. The mixture was refluxed a further 10 minutes and then cooled, filtered and the benzene removed to leave a phosphorane of formula: ##STR13## as residue.

The phosphorane was then reacted with t.-butyl caronaldehyde in dichloromethane as described in Example 10 to give a compound b.p. 130°/3 mm., n_(D) 1.4714 identified as in Example 10 as being of formula II where R³ =COOCH₃, R² =C₂ H₅, R¹ =H and R=t.-butyl. (Compound P19/F¹).

The above procedure was also repeated replacing the methyl chloroformate by ethyl and n-propyl chloroformate respectively when the following compounds of formula II were obtained.

    ______________________________________                                         R.sup.3       R.sup.2                                                                               R.sup.1                                                                               R     b.p.   n.sub.D                               ______________________________________                                         P19/G.sup.1                                                                           COOC.sub.2 H.sub.5                                                                        C.sub.2 H.sub.5                                                                       H    t.-butyl                                                                             114-116°/                                                                      1.4682                                                                  1 mm.                                      P19/H.sup.1                                                                           COOn-C.sub.3 H.sub.7                                                                      C.sub.2 H.sub.5                                                                       H    t.-butyl                                                                               120°/                                                                        1.4683                                                                  1 mm.                                      ______________________________________                                    

EXAMPLE 14

The compound of formula II where R³ =n-propoxy carbonyl, R² =CH₃ and R=t.-butyl (0.393 g.) described in Example 12 was refluxed 2 hours with toluene 4-sulphonic acid (47.2 mg.) in benzene (11.5 ml.). The solution was cooled and the resulting acid (R³ =n-propoxycarbonyl, R² =CH₃, R=H) crystallised out. Dry pyridine (0.127 g., 131 μl.) and thionyl chloride (0.158 g. 96 μl) were added and the mixture left to stand for 2 hours at about 20° when the corresponding acid chloride formed.

A solution of 5-benzyl-3-furylmethyl alcohol (275 mg.) and pyridine (0.105 g., 108 μl.) in benzene (8 ml.) was added and the solution left to stand overnight. The resulting solution was passed through a column of neutral alumina and then evaporated to give 550 mg. of a compound of formula II where R³ =n-propoxycarbonyl, R² =CH₃ and R=5-benzyl-3-furylmethyl, n_(D) 1.5125. (Compound P19/E). The structure of the ester as being in accordance with formula II was confirmed by NMR spectroscopy and gas/liquid chromatography.

The following esters were prepared by similar methods.

    ______________________________________                                         Compound    R.sup.2   R.sup.3    n.sub.D                                       ______________________________________                                         P19/A       H         COOCH.sub.3                                                                               1.5262                                        P19/D       H         COOC.sub.2 H.sub.5                                                                        1.5298                                        P19/C       H         COOn-C.sub.3 H.sub.7                                                                      1.5278                                        P19/D       CH.sub.3  COOC.sub.2 H.sub.5                                                                        1.5235                                        P19/E       CH.sub.3  COOn-C.sub.3 H.sub.7                                                                      1.5125                                        P19/F       C.sub.2 H.sub.5                                                                          COOCH.sub.3                                                                               1.5228                                        P19/G       C.sub.2 H.sub.5                                                                          COOC.sub.2 H.sub.5                                                                        1.5193                                        P19/H       C.sub.2 H.sub.5                                                                          COOn-C.sub.3 H.sub.7                                                                      1.5190                                        ______________________________________                                    

Compounds P19/A to P19/H are all compounds of formula II where R=5-benzyl-3-furylmethyl.

EXAMPLE 15

t.-Butyl-(1R)-trans-caronaldehyde (1.0 g.) (obtained by ozonolysis of the t.-butyl ester of (1R)-trans-chrysanthemic acid) and triphenyl phosphine (2.65 g.) dissolved in dry carbon tetrachloride (10 ml.) were heated, under nitrogen with stirring, at 60° for 7 hours. The reaction mixture was evaporated under reduced pressure and the residue extracted with diethyl ether (≠30 ml.). The organic extract was washed with water, dried (over Na₂ SO₄) and evaporated. The residue was extracted with petroleum ether (40°-60°) and the solution evaporated and distilled yielding crude product (0.77 g.) (b.p. 100°/1 mm.), which was purified by crystallisation to give t-butyl-(1R)-trans-2,2-dimethyl-3-(2,2-dichlorovinyl) cyclopropane carboxylate m.p. 52°-3° (Compound P21/A').

EXAMPLE 16

Triphenyl phosphine (1.32 g.) was added to a well stirred solution of carbon tetrabromide (0.84 g.) in dry dichloromethane (15 ml.). t.-Butyl-(1R)-trans-caronaldehyde (0.5 g.) was added and the solution was stirred overnight at room temperature. After working up as described in Example 15, the crude product was distilled yielding two fractions (1) b.p. 83°-90°/0.7 mm, (0.15 g.), n_(D) 1.4749 (2) b.p. 90°-107°/0.7 mm, (0.24 g.), n_(D) 1.4910. The second fraction was shown (glc) to contain ≃95% of the desired t-butyl-(1R)-trans-2,2-dimethyl-3-(2,2-dibromovinyl) cyclopropane carboxylate. (Compound P21/B').

EXAMPLE 17

The t-butyl ester described in Example 15 (280 mg.), was heated at reflux with toluene-4-sulphonic acid (55 mg.) in dry benzene (10 ml.) for 1.5 hour and cooled to give a solution of the corresponding acid. Pyridine (108.5 mg.) and thionyl chloride (126 mg.) were added and the mixture left to stand at room temperature for 2 hours. A solution of pyridine (83.5 mg.) and 5-benzyl-3-furylmethyl alcohol (219 mg.) in dry benzene (5 ml.) was added and the mixture left to stand overnight. After chromatography on neutral alumina, the solution was evaporated to yield 296 mg. of a (1R) trans compound of formula II where R³ =Cl, R² =Cl, R¹ =H and R=5-benzyl-3-furylmethyl. This ester, designated ester P21A, has n_(D) 1.54031.

The above procedure was repeated with ester P21/B' described in Example 16 to give (1R)trans ester P21/B where R² =R³ =Br, R¹ =H, R=5benzyl-3-furylmethyl, n_(D) 1.5462.

EXAMPLE 18

The conversion of the acid to the acid chloride and subsequent esterification using 5-benzyl-3-furylmethyl alcohol as described in Example 17 was repeated replacing the (1R)-trans acid by other isomers of the acid, and 3-phenoxybenzyl alcohol, 3-benzyl benzyl alcohol, (+)-pyrethrolone, 5-propargyl-2-furylmethyl alcohol, 2,3,4,5-tetrahydrophthalimidomethyl alcohol, α-ethynyl-3-phenoxybenzyl alcohol or (±)-allethrolone were used as the alcohol to give the following esters of formula II.

    ______________________________________                                         Compound                                                                               R.sup.3                                                                              R.sup.2                                                                              R.sup.1                                                                            Configuration                                                                            m.p.°                                                                        n.sub.D                                 ______________________________________                                         P21C    Cl    Cl    H   (1RS)-trans                                                                              61   1.5518                                  P21D    Cl    Cl    H   (1RS)-cis 43   1.5485                                  P21E    Cl    Cl    H   (1RS)-cis-trans                                                                          48.58                                                                               1.5445                                  P21F    Cl    Cl    H   (1RS)-trans    1.5607                                  P21G    Cl    Cl    H   (1RS)-cis      1.5654                                  P21H    Cl    Cl    H   (1RS)-cis-trans                                                                               1.5694                                  P21I    Cl    Cl    H   (1RS)-trans    1.5633                                  P21J    Cl    Cl    H   (1RS)-cis      1.5654                                  P21K    Cl    Cl    H   (1RS)-cis-trans                                                                               1.5701                                  P21M    Cl    Cl    H   (1RS)-trans    1.5324                                  P21Q    Cl    Cl    H   (1RS)-trans    1.5237(n.sub.D.sup.23)                  P21S    Cl    Cl    H   (1RS)-trans    1.5333(n.sub.D.sup.23)                  ME7     Br    Br    H   (1R)-cis       1.5895                                  ME9     F     F     H   (1R)-trans     1.4889                                  ME10    F     F     H   (1R)-cis       1.4915                                  ______________________________________                                    

In compounds P21C, P21D and P21E, R=5-benzyl-3-furylmethyl, in compounds P21F, P21G and P21H, R is 3-phenoxybenzyl, in compounds P21I, P21J and P21K, R is 3-benzylbenzyl, in 21M, R is (+)-pyrethronyl, in P21Q, R is 5-propargyl-2-furylmethyl, in P21S, R is 3,4,5,6-tetrahydrophthalimidomethyl, in ME7, R is α-ethynyl-3-phenoxybenzyl, and in ME9 and ME10, R is (±)-allethronyl.

The starting acid was prepared by a variant on the conventional chrysanthemic acid synthesis using ethyl diazoacetate in which, in this case, 1,1-dichloro-4-methyl-1,3-pentadiene was reacted with ethyldiazoacetate in the presence of the copper catalyst and the resulting ethyl (1RS)-cis-trans-2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane carboxylate hydrolysed to the free acid. The cis- and trans-isomers can be separated from one another by selective crystallisation from n-hexane in which the cis isomer is more soluble. The isomeric mixture was dissolved in hexane at room temperature and cooled to 0° or -20° C., when the trans-isomer precipitates. This precipitate was ground up, washed with a small volume of hexane at room temperature and the residue recrystallised again from hexane at 0° or -20° C., to give the trans-isomer as a residue. The cis-isomer is recovered from the hexane solution.

EXAMPLE 19

(a) 5-Benzyl-3-furylaldehyde

Chromium trioxide (3.00 g.) was added to a stirred solution of pyridine (4.75 g.) in dry methylene chloride (75 ml.), and stirring was continued for 15 minutes. 5-Benzyl-3-furylmethyl alcohol (0.94 g.) was added and the mixture stirred for 15 minutes. The mixture was filtered and the residue washed with ether (100 ml). The filtrate and washings were combined and washed with 5% sodium hydroxide solution (3×50 ml.), 2.5N hydrochloric acid (50 ml.) and 5% sodium carbonate solution (50 ml.) and dried (Na₂ SO₄).

Yield=(0.53 g.), b.p.116°/0.8 mm.Hg, n_(D) =1.5652.

(b) (αRS)-Cyano-5-benzyl-3-furylmethyl alcohol

The aldehyde (1) (0.53 g.) was added to a solution of potassium cyanide (0.3 g.) in water (3 ml.) and dioxan (5 ml.) was added to effect solution. The solution was stirred for 10 minutes at 15° C., when 40% sulphuric acid (1 ml.) was added dropwise, stirring being continued for a further 10 minutes. The mixture was extracted with carbontetrachloride (50 ml.) and dried (Na₂ SO₄). Evaporation yielded the product (0.53 g.), n_(D) 1.5377. (The structure was confirmed by NMR).

(c) (αRS)-Cyano-5-benzyl-3-furylmethyl-(1RS)-cis-trans-3-(2,2-dichlorovinyl)-2,2-dimethyl cyclopropane carboxylate (Compound P21/N).

A mixture of the alcohol (265 mg.) prepared as described above, and 80 mg. pyridine in 10 ml. dry benzene was added to 227 mg. of (1RS)-cis-trans-3-(2,2-dichlorovinyl)-2,2-dimethyl cyclopropane carboxylic acid chloride in 10 ml. dry benzene. The resulting mixture was left overnight and then column chromatographed on neutral alumina. Evaporation of solvent gave 0.31 g. of Compound P21/N, n_(D) 1.5428. (Structure confirmed by NMR).

EXAMPLE 20

(a) 3-Phenoxybenzaldehyde

Chromium trioxide (3.00 g.) was added to a stirred solution of pyridine (4.75 g.) in dry methylene chloride (75 ml.), and stirring was continued for a further 15 minutes. 3-Phenoxybenzyl alcohol (1 g.) in methylene chloride (5 ml.) was added, the mixture stirred for a further 15 minutes, decanted and the residue washed with diethyl ether (100 ml.). The filtrate was washed with 5% sodium hydroxide solution (3×50 ml), 2.5 NHCl (50 ml.) and 5% sodium carbonate solution (50 ml.) and dried over Na₂ SO₄ to give 3-phenoxy-benzaldehyde. Alternatively the alcohol can be oxidized using Jones' reagent, a similar yield of aldehyde being obtained.

Yield (0.80 g.), b.p. 126°/0.8 mm.Hg, n_(D) =1.5984.

(b) (αRS)-Cyano-3-phenoxybenzyl alcohol

3-Phenoxybenzaldehyde (0.8 g.) was added to a solution of potassium cyanide (0.3 g.) in water (1 ml.) at 15°. Slowly during 10 minutes 40% sulphuric acid (1 ml.) was added dropwise, stirring being continued for a further 15 minutes. The mixture was extracted with carbon tetrachloride (40 ml.); dried (Na₂ SO₄) and evaporated to yield 0.64 g. of (αRS)-α-cyano-3-phenoxy-benzyl alcohol. n_(D) =1.5832 (Structure confirmed by NMR).

(c) This α-cyano alcohol described above (247 mg.), pyridine (79 mg.) and (1RS)-cis-trans-2,2-dimethyl-3-(2,2-dichlorovinyl)cyclopropane carboxylic acid chloride (227 mg.) were reacted at 20° C., in benzene (20 ml.) solution for 18 hours, which after chromatography on neutral alumina and evaporation of the solvent yielded (αRS)-cyano-3-phenoxybenzyl-(1RS)-cis-trans-3-(2,2-dichlorovinyl)-2,2-dimethyl cyclopropane carboxylate (Compound P21/P) (260 mg.), n_(D) 1.5561. (Structure confirmed by NMR).

EXAMPLE 21

(a) 3-Benzylbenzaldehyde

Benzylbenzyl alcohol (1 g.) was oxidised using the chromium trioxide/pyridine complex as described in Example 20 (a) yielding the aldehyde (0.67 g.), b.p. 124° C./0.2 mm, n_(D) 20=1.6010.

(b) (αRS)-Cyano-3-benzylbenzyl alcohol

The prepared aldehyde (0.67 g.) underwent the reactions described in Example 20 (b) to form the required cyanohydrin (0.41 g.), n_(D) 20=1.5703.

(αRS)-Cyano-3-benzylbenzyl-(1RS)-cis-trans-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate (Compound P21/Q) of n_(D) 1.5462 was prepared from the alcohol of (b) above and the acid chloride following the procedure of Example 20 (c).

EXAMPLE 22

(a) 3'-Phenoxybenzyl-3-formyl-2,2-dimethylcyclopropane carboxylate.

3-Phenoxybenzyl-(1R)-trans-chrysanthemate (2.0 g.) in methanol (500 g.) at -70° C., was subjected to a stream of ozone for 30 minutes. Nitrogen was passed through the solution and dimethyl sulphide (1.5 g.) added. It was allowed to warm to room temperature and stirred overnight. The solvent was evaporated and acetone (30 ml.) and 30% acetic acid (20 ml.) were added, the solution being allowed to stand for 30 minutes at 80° C. It was poured onto water (200 ml.) and extracted with ether (200 ml.). After washing with sodium carbonate solution the organic solution was dried (Na₂ SO₄) and evaporated to give the title aldehyde. Yield (1.69 g.) n_(D) 20=1.5558.

(b) The procedure described in Example 15 was repeated using 3'-phenoxybenzyl-3-formyl-2,2-dimethyl cyclopropane carboxylate in place of t.-butyl caronaldehyde to give compound P21F (see Example 18) directly.

EXAMPLE 23

Triphenyl phosphine (13 g.) was dissolved in dry benzene (60 ml.) and methyl bromoacetate (8.3 g.) was added dropwise. The solution was heated at 70° C., for 2 days, and then cooled and filtered. The residue was washed with benzene and dried to give about 16 g. of (methoxycarbonyl methyl)triphenylphosphonium bromide. The phosphonium salt (B 10 g.) was dissolved in water (250 ml.) and 5% aqueous sodium hydroxide was added dropwise with stirring until the solution became alkaline to litmus. The resulting precipitate was filtered off, washed with water and dried. Crystallisation from ethyl acetate/petroleum spirit gave (methoxycarbonyl methylene) triphenyl phosphorane as a colourless solid in about 80% yield.

(Methoxycarbonylmethyl)triphenylphosphorane (3.34 g.) in methylene chloride (70 ml.) was cooled to -70° C., triethylamine (1.01 g.) was added with stirring followed by chlorine (0.77 g.) in CCl₄ (11 mls). Stirring was continued for 30 minutes at this temperature and for 1 hour while the reaction mixture warmed to room temperature. The reaction mixture was washed with water (3×50 ml.), dried over Na₂ SO₄ and evaporated to yield 2.8 g. of chlorinated phosphorane/Ph₃ P=C(Cl)COOMe.

A mixture of t.-butyl-(1R)trans-caronaldehyde (from ozonolysis of t.-butyl ester of (1R)-trans-chrysanthemic acid) (0.7 g.) and the chlorinated phosphorane (1.3 g.) in 10 ml. dry benzene was refluxed for one hour. After distillation of the benzene, the resulting product was distilled under reduced pressure to give t.-butyl-2,2-dimethyl-3-(2-chloro-2-carbomethoxyvinyl)-cyclopropyl carboxylate, b.p. 110° C./0.4 mm, n_(D) ²⁰ 1.4749 (Yield, 0.65 g.).

This compound was designated Compound P24A'.

EXAMPLE 24

The procedure described in Example 23 was repeated replacing the methyl bromoacetate by ethylbromoacetate or propylbromoacetate and by replacing the methylbromoacetate by ethylbromoacetate and replacing chlorine by bromine in the halogenation of the phosphorane step. The following compounds of formula II were obtained.

    ______________________________________                                         Compound                                                                               R       R.sup.3    R.sup.2                                                                             b.p.     n.sub.D.sup.20                        ______________________________________                                         P24B'   t.-butyl                                                                               COOC.sub.2 H.sub.5                                                                        Cl   110-112° C./                                                                     1.4883                                                                0.4 mm                                         P24C'   t.-butyl                                                                               COOn-C.sub.3 H.sub.7                                                                      Cl   160-180° C./                                                                     1.4688                                                                0.8 mm                                         P24D'   t.-butyl                                                                               COOC.sub.2 H.sub.5                                                                        Br   120-124° C./                                                                     1.4830                                                                0.04 mm                                        ______________________________________                                    

EXAMPLE 25

A mixture of compound P24A' of Example 23 (320 mg.) and toluene-4-sulphonic acid (50 mg.) in dry benzene (10 ml.) were refluxed for approximately 2 hours and then cooled. 2,2-Dimethyl-3-(2-chloro-2-carbomethoxyvinyl)-cyclopropane carboxylic acid was identified in the solution by NMR. Pyridine (111 mg., 114 microliters) and thionyl chloride (132 mg., 80 microliters) were added to the solution of the carboxylic acid and the mixture was left for 3 hours at room temperatures. 2,2-Dimethyl-3-(2-chloro-2-carboxymethylvinyl)-cyclopropane carboxylic acid chloride was identified in the solution by NMR. A solution of 5-benzyl-3-furylmethyl alcohol (210 mg.) and pyridine (88 mg., 90 microliters) in dry benzene (5 ml.) was added and the mixture left overnight at room temperature. The solution was then run through a column of neutral alumina and eluted with benzene to give 200 mg. of the 5-benzyl-3-furylmethyl ester of 2,2-dimethyl-3-(2-chloro-2-carboxymethoxyvinyl)-cyclopropane carboxylic acid, n_(D) ²⁰ 1.5398. This compound was designated compound P24A.

EXAMPLE 26

The procedure described in Example 25 was repeated using compounds P24B', P24C' and P24D' of Example 24 and the following compounds of formula II were obtained.

    ______________________________________                                         Compound     R.sup.3      R.sup.2                                                                              n.sub.D.sup.20                                 ______________________________________                                         P24B         COOC.sub.2 H.sub.5                                                                          Cl    1.5404                                         P24C         COOn-C.sub.3 H.sub.7                                                                        Cl    1.5332                                         P24D         COOC.sub.2 H.sub.5                                                                          Br    1.5366                                         ______________________________________                                    

The above three compounds are compounds of formula II where R represents 5-benzyl-3-furylmethyl.

EXAMPLE 27

Methyl-(1R)-cis-caronaldehyde was obtained by ozonolysis of methyl (1R)-cis-chrysanthemate. The procedure described in Example 16 was then repeated using 5.3 g. triphenylphosphine, 3.36 g. carbon tetrabromide and 60 mls. dry dichloromethane and 1.5 g. methyl-(1R)-cis-caronaldehyde. The reaction product was then refluxed 3 hours with 9 mls. acetic acid, 6 mls. concentrated HBr and 3 mls. water and then diluted with water and extracted with ether. The organic solution was extracted with dilute sodium hydroxide and this extract acidified and extracted with ether and evaporated to give a residue of (1R)cis-2,2-dimethyl-3-(2,2-dibromovinyl)-cyclopropane carboxylic acid.

The carboxylic acid described above was converted to its acid chloride by reaction with thionyl chloride in pyridine as described in Example 17 and the resulting acid chloride reacted with 3-phenoxybenzyl alcohol in dry benzene in the presence of pyridine as described in Example 17 to give 3-phenoxybenzyl(1R)cis-2,2-dimethyl-3-(2,2-dibromovinyl)-cyclopropane carboxylate, m.p. 93°, n_(D) 1.5848 (Compound P29A).

The esterification described above was repeated replacing 3-phenoxybenzyl alcohol by (αRS)-cyano-3-phenoxybenzyl alcohol to give (αRS)-cyano-3-phenoxybenzyl(1R)cis-2,2-dimethyl-3-(2,2-dibromovinyl)cyclopropane carboxylate, n_(D) 1.5732. (Compound P29B). Compound P29B has [α]_(D) ²⁰ =-1° (C=0.4 in ethanol). N.M.R. peaks associated with the C-H group (carbon atom bearing the α-cyano substituent) γ=3.65 and 3.72 (equal areas).

0.6 grams of the racemate was dissolved in 25 ml hexane and maintained at -20° C. until precipitation of crystals was complete. The crystals were then filtered off and recrystallised from hexane to give (αS)-cyano-3-phenoxybenzyl (1R)cis-2,2-dimethyl-3-(2,2-dibromovinyl)cyclopropane carboxylate in 0.25 g yield. The physical characteristics of this crystalline isomer are as follows:

m.p. 100° C.

[α]_(D) ²⁰ +16° (C=0.4 in ethanol).

N.M.R. Peaks associated with the C-H group (carbon atom bearing the α-cyano substituent) γ=3.65 but no peak at γ=3.72.

The mother liquors were combined and evaporated to dryness to give 0.32 g of the non-crystalline isomer, (αR)-cyano-3-phenoxybenzyl (1R)cis-2,2-dimethyl-3-(2,2-dibromovinyl)cyclopropane carboxylate having the following properties:

n_(D) 1.5749.

[α]_(D) ²⁰ -15° (C=0.4 ethanol).

N.M.R. Peaks associated with the C-H bond (carbon atom bearing to the α-cyano group) γ=3.72 with a small peak (20% of the 3.72 peak) at γ=3.65 attributable to the crystalline isomer.

EXAMPLE 28

The esterification procedures described in Example 27 were repeated replacing the (1R)-cis-dibromovinyl acid by (1R)trans-2,2-dimethyl-3-(2,2-dibromovinyl)-cyclopropane carboxylic acid (obtained as described in Example 16), (1R)trans-2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane carboxylic acid (prepared as described in Example 15) and (1RS)-cis-trans-2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane carboxylic acid prepared as described in Example 18. The following esters were prepared:

3-phenoxyphenyl (1R)trans-2,2-dimethyl-3-(2,2-dibromovinyl)-cyclopropane carboxylate, n_(D) 1.5828 (Compound P29C).

(αRS)-cyano-3-phenoxybenzyl (1R)trans-2,2-dimethyl-3-(2,2-dibromovinyl)-cyclopropane carboxylate, n_(D) 1.5664 (Compound P29D).

(αRS)-cyano-3-phenoxybenzyl(1R)trans-2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane carboxylate n_(D) 1.5498 (Compound P29E).

(αRS)-cyano-3-phenoxybenzyl(1RS)-cis-trans-2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane carboxylate, n_(D) 1.5632 (Compound P29F).

(αRS)-cyano-3-phenoxybenzyl(1RS)-cis-2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane carboxylate, n_(D) 1.5597 (Compound P29G).

(αRS)-cyano-3-phenoxybenzyl(1RS)-trans-2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane carboxylate, n_(D) 1.5551 (Compound P29H).

(αRS)-cyano-3-phenoxybenzyl (1R)-cis-2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane carboxylate, n_(D) 1.5622 (Compound P29J).

(αRS)-cyano-3-phenoxybenzyl (1S)-cis-2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane carboxylate, n_(D) 1.5520 (Compound P29K).

The required isomer of the acid for the last four-mentioned esters was obtained by resolution as described in Example 32.

EXAMPLE 29

(1R)Trans-3-(2,2-difluorovinyl)-2,2-dimethyl-cyclopropane carboxylic acid.

(a) A mixture of freshly distilled, dry, dimethyl formamide (20 ml), triphenylphosphine (7.9 g), methyl (1R)trans-caronaldehyde (3.0 g) and the sodium salt of chlorodifluoro acetic acid (3.6 g) were heated at 90° C. with stirring for 20 hours. Water (60 ml) were then added and the solution extracted with 2×30 ml portions of diethylether. The combined ethereal extracts were washed with water, saturated sodium carbonate solution, saturated sodium chloride solution, and then dried over sodium sulphate and the ether distilled off. Distillation of the residue gave 2.25 g of methyl (1R)-trans-3-(2,2-difluorovinyl)-2,2-dimethyl cyclopropane carboxylate, b.p. 63° C./20 mm, n_(D) 1.4209.

(b) An alkaline solution was prepared by dissolving sodium hydroxide (200 mg) in water (1 ml) and ethanol (10 ml) was added. The methyl ester described above (0.5 g) was stirred into the alkaline solution and the mixture was refluxed for 1 hour. The solvents were removed under reduced pressure and water (30 ml) added. The solution was washed with 2×20 ml portions of diethylether and acidified with concentrated hydrochloric acid. The mixture was extracted with 2×30 ml portions of diethylether, washed with saturated sodium chloride solution, dried over sodium sulphate and the solvents evaporated to leave 410 mg of (1R)-trans-3-(2,2-difluorovinyl)-2,2-dimethyl-cyclopropane carboxylic acid as an oil having n_(D) 1.4400.

EXAMPLE 30

(1R)Cis-3-(2,2-difluorovinyl)-2,2-dimethyl-cyclopropane carboxylic acid.

(a) The procedure described in Example 29 (a) above was repeated using 1.5 g methyl (1R)-cis-caronaldehyde, 2.92 g triphenylphosphine, 1.2 g sodium chlorodifluoro acetate and 7 ml dimethylformamide. The residue obtained after evaporating the final diethyl ether extract was itself extracted with 3×40 ml portions of petroleum ether and the petroleum ether evaporated and the residue distilled to give 440 mg of methyl (1R)-cis-3-(2,2-difluorovinyl)-2,2-dimethyl-cyclopropane carboxylate b.p. 74°-78° C./20 mm, n_(D) 1.4288.

(b) The methyl ester obtained above (380 mg) was added to a solution of sodium hydroxide (200 mg) in water (1 ml) and ethanol (10 ml). The mixture was refluxed for 1 hour with stirring and the solvents removed under reduced pressure. Water (50 ml) was then added and the solution washed with 20 ml diethylether, acidified with concentrated hydrochloric acid and extracted with diethyl ether. The ethereal extract was washed with saturated sodium chloride, dried over sodium sulphate and evaporated to give 290 mg of (1R)-cis-3-(2,2-difluorovinyl)-2,2-dimethyl-cyclopropane carboxylic acid, n_(D) 1.4456.

EXAMPLE 31

The acids described in Examples 29 and 30 were esterified with 5-benzyl-3-furylmethyl alcohol, 3-phenoxybenzyl alcohol and (αRS)-cyano-3-phenoxybenzyl alcohol by the following procedure. A solution of the acid (110 mg) in benzene (5 ml) was treated with pyridine (50 μl) and thionyl chloride (45 μl) and left to stand for three hours at the end of which time, the acid has been converted into its acid chloride. A solution of 3-phenoxybenzyl alcohol (137 mg) or an equivalent quantity of the other alcoholic and pyridine (50 μl) in benzene (5 ml) was added to the acid chloride and the mixture left to stand overnight. The desired ester was recovered from the solution by passing it through a column of neutral alumina and eluting the column with benzene. The eluate was evaporated to leave the ester as an oil, the following results being obtained.

    ______________________________________                                         Compound                                                                               Acid       Alcohol         n.sub.D                                     ______________________________________                                         P31A    (1R)-trans 5-benzyl-3-furylmethyl                                                                         1.5142                                      P31B    (1R)-trans 3-phenoxybenzyl 1.5293                                      P31C    (1R)-trans (αRS)-cyano-3-phenoxy-                                                                   1.5330                                                         benzyl                                                      P31D    (1R)-cis   5-benzyl-3-furylmethyl                                                                         1.5136                                      P31E    (1R)-cis   3-phenoxybenzyl 1.5349                                      P31F    (1R)-cis   (αRS)-cyano-3-phenoxy-                                                                   1.5355                                                         benzyl                                                      ______________________________________                                    

EXAMPLE 32

(1RS)-cis-trans-2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane carboxylic acid, prepared by reacting ethyl diazoacetate with 1,1-dichloro-4-methyl-penta-1,3-diene and hydrolysing the resulting ethyl ester, was separated into the (1RS)-cis and (1RS)-trans isomers by selective crystallisation in n-hexane, in which the cis isomer is more soluble. The substantially pure cis and trans isomers were then resolved into their individual optical isomers by the following procedure.

Resolution of (1RS)-cis-2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane carboxylic acid. The (1RS)-cis acid (14.6 g) in benzene (250 ml), and (+)-α-methylbenzylamine (8.47 g) in benzene (30 ml) were mixed at 50°, and allowed to cool to 20° overnight. The precipitate (13.2 g, 58% required isomer) was recrystallised 3 times from benzene to give the (+)-α-methyl benzylamine salt of the (1S)-cis acid (1.7 g) m.p. 135°, [α]_(D) -17.1° (C, 1.6 in EtOH) was isolated. Repetition, using (-)-α-methylbenzylamine gave, after 3 crystallisations, the (-)-α-methylbenzylamine salt of the (1R)-cis acid (6.1 g) m.p. 147° [α]_(D) -26.1° (C, 1.9 in EtOH) and from the mother liquors the (-)-α-methylbenzylamine salt of the (1S)-cis acid (3.8 g) m.p. 139° [α]_(D) +14.8° (C, 2.0 in EtOH).

Each of the four salts was shaken with benzene (50 ml) and 3N HCl (50 ml) and the benzene layer processed to give the resolved acids. Thus were obtained (1S)-cis-2,2-dimethyl-3-(2,2-dichlorovinyl) cyclopropane carboxylic acid (4.6 g) m.p. 90° [α]_(D) -26.9° (c, 1.7 in CHCl₃) and (1R)-cis-2,2-dimethyl-3-(2,2-dichlorovinyl) cyclopropane carboxylic acid (3.9 g) m.p. 90° [α]_(D) +27.2° (c, 2.1 in CHCl₃).

Resolution of (1RS)-trans-2,2-dimethyl-3-(2,2-dichlorovinyl)cyclopropane carboxylic acid. The (1RS)-trans acid (15.6 g) in benzene (180 ml and L-(+)-threo-1-p-nitro-phenyl-2-N,N-dimethylaminopropane-1,3-diol (18.0 g) in benzene (180 ml) were mixed at 50° and cooled to 20° during 2 days. The precipitate (14.2 g) was recrystallised 3 times from trichloroethylene to give the L-(+)-threo-1-p-nitrophenyl-2-N,N-dimethylaminopropane-1,3-diol salt of (1S)-trans-2,2-dimethyl-3-(2,2-dichlorovinyl) cyclopropanecarboxylic acid (8.9 g) m.p. 129°-131° [α]_(D) +7.4° (c, 2.1 in EtOH). Correspondingly D-(-)-threo-1-p-nitrophenyl-2-N,N-dimethylaminopropane-1,3-diol gave the salt with the (1R)-trans acid (9.4 g) m.p. 129°-131°, [α]_(D) -7.3° (c, 2.0 in EtOH). Decomposition of the salts with 3N HCl as described for the cis acids gave (1S)-trans-2,2-dimethyl-3-(2,2-dichlorovinyl) cyclopropane carboxylic acid (3.8 g) m.p. 68°-73°, [α]_(D) -34.6° (c, 1.9 in EtOH) and (1R)-trans-2,2-dimethyl-3-(2,2-dichlorovinyl) cyclopropane carboxylic acid (4.1 g) m.p. 69°-73°, [α]_(D) +33.0° (c, 2.0 in EtOH).

The (1R)-cis and (1R)trans acids were converted to their acid chloride and reacted with 3-phenoxybenzyl alcohol by the procedure described in Example 1 to give the 3-phenoxybenzyl ester of (1R)-cis and of (1R)-trans-2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane carboxylic acid, compounds P29L and P29M respectively.

The (1R)-cis acid was also esterified with 5-benzyl-3-furylmethyl alcohol by the same procedure to give compound P29N, 5-benzyl-3-furylmethyl (1R)-cis-2,2-dimethyl-3-(2,2-dichlorovinyl) cyclopropane carboxylate.

The toxicity of these new esters was tested by the procedure described in detail in our above mentioned application and the following results were obtained:

    ______________________________________                                                        Relative Toxicity                                               Compounds        Houseflies                                                                               Mustard Beetles                                     ______________________________________                                         5-benzyl-3-furylmethyl                                                                          1,000     1,000                                               (1R)-trans-chrysanthemate                                                      (Bioresmethrin)                                                                P29L             1,600     1,400                                               P29M               740     2,100                                               P29N             2,600     2,200                                               ______________________________________                                    

The toxicity of compounds P29L and P29M relative to bioresmethrin was also determined against the American cockroach, Periplaneta americana L. with the following results.

    ______________________________________                                         Compound      Relative Toxicity                                                ______________________________________                                         Bioresmethrin 100*                                                             P29L          2,100                                                            P29M          800                                                              ______________________________________                                          *LD.sub.50 = 2.5 μg/insect                                            

EXAMPLE 33

3,4,5,6-Tetrahydrophthalimidomethyl alcohol was esterified by the procedure described in Example 17 using the (1R)trans-isomer of 3-(2,2-difluorovinyl)-2,2-dimethylcyclopropanecarboxylic acid chloride prepared by reacting the acid with thionyl chloride. The resulting ester, designated DP 870 has n_(D) ²⁰ 1.5015. The corresponding (1R)cis-isomer was similarly prepared and is designated DP 891. This is a colourless crystalline solid, m.p. 97°-99° C.

These esters were tested for their knock-down effect on houseflies using a modified Kearns & March technique. The basic technique (cf. soap 19 page 101 and 128 (1943)) was modified by using a chamber having two sprayers at each end, each discharging 1 ml of test solvent every 5 seconds. 0.1 ml of a known solution of test compound was introduced into each sprayer and 200 flies were introduced. The test compound was sprayed for 5 seconds and knock-down counts taken at 1 minute intervals for ten minutes. From these results, KD₅₀ values were calculated. For comparative purposes, similar tests were carried out using natural pyrethrin (25% w/w pyrethum extract) and bioallethrin. The following results were obtained.

    ______________________________________                                                      % Concentration                                                   Test Compound                                                                               giving KD.sub.50 of 4 minutes                                     ______________________________________                                         DP 870       0.04                                                              DP 891       0.014                                                             Pyrethrins   0.032                                                             Bioallethrin 0.054                                                             ______________________________________                                    

The knock-down effect against cockroaches was shown in the following tests. The compound under test was dissolved in odourless kerosene and sprayed on male Blattella germanica at various concentrations. The KD₅₀ for the compounds were calculated to be as follows:

    ______________________________________                                                      % Concentration (w/v)                                             Test Compound                                                                               giving KD.sub.50 at 5 minutes                                     ______________________________________                                         DP 870       0.0057                                                            Bioallethrin 0.064                                                             S-Bioallethrin                                                                              0.033                                                             ______________________________________                                    

The insecticidal activity of DP 870 against houseflies was tested by spraying M. domestica in a Kearns and March chamber with a solution of a compound in odourless kerosene, and LD₅₀ values calculated. The activity of DP 870 synergised with piperonylbutoxide was also measured and the results compared with the LD₅₀ value for compound P21H of Example 18.

    ______________________________________                                         Test Compound     LD.sub.50 μg/female                                       ______________________________________                                         DP 870            0.09                                                         DP 870 plus piperonyl-                                                                           0.04                                                         butoxide (1:5 w/w)                                                             Compound P21H of  0.022                                                        Example 18 (Permethrin)                                                        ______________________________________                                    

EXAMPLE 34

4-Phenoxybut-2-ynyl(1R)cis-3-(2,2-difluorovinyl)-2,2-dimethylcyclopropane carboxylate

4-Phenoxybut-2-ynol (0.28 g) in benzene (2.8 ml) and pyridine (0.15 g) was treated with a solution of (1R)-cis-3-(2,2-difluorovinyl)-2,2-dimethylcyclopropanecarboxylic acid chloride (0.33 g) in benzene (3 ml) with cooling. After 5 hours, the mixture was filtered through a column of alumina (3 g) and eluted with benzene. Evaporation of the eluate gave the title ester n_(D) ²⁰ 1.5121 (Compound ME3).

Similarly prepared were:

4-Phenoxybut-2-ynyl (1R)-trans-3-(2,2-difluorovinyl)-2,2-dimethylcyclopropane carboxylate n_(D) ²⁰ 1.5080 (Compound ME4);

4-Phenoxybut-2-ynyl (1RS)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate n_(D) ²⁰ 1.5362 (Compound ME5);

4-Phenoxybut-2-ynyl (1R)cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylate, n_(D) ²⁰ 1.5730 (Compound ME6).

EXAMPLE 35

2-Benzylcyclopent-2-enone (16.0 g) and recrystallised N-bromosuccinimide (16 g) in dry CCl₄ (100 ml) were refluxed until the NBS disappeared completely to form 4-bromo-2-benzylcyclopent-2-enone. When the reaction was complete, the product was filtered and refluxed in the dark with the silver salt of 2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane carboxylic acid (34.6 g) for 5 hours. The reaction mixture was filtered through a column of alumina and eluted with benzene. Distillation of the eluate gave (±)-2-benzycyclopentenon-4-yl(1RS)-cis,trans-3,(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate. This ester was designated ME8.

EXAMPLE 36

(a) Preparation of 3-benzoylbenzaldehyde

3-Methylbenzophenone (6.0 g), N-bromosuccinimide (10.9 g) and dry carbon tetrachloride (100 ml) were heated at reflux for 8 hours. (≃70% of dibromide was present). The mixture was cooled, filtered and the filtrate evaporated to yield the crude dibromide.

Sodium hydroxide (2.35 g) in ethanol (30 ml) was heated to boiling with formic acid (2.7 g) and water was added (≃5 ml) to form a homogeneous solution. This was poured onto the above crude dibromide in ethanol (40 ml) and the whole was refluxed for 48 hours. Concentrated hydrochloric acid (1 ml) was added and refluxing was continued for 1 hour further. The solution was concentrated (≃30 ml), treated with water and extracted with ether and the ethereal solution washed with 10% sodium carbonate and sodium chloride solutions, dried over sodium sulphate and evaporated. Purification of the crude mixture via the bisulphite complex yielded the pure aldehyde (1.8 g) b.p. 160°-170° C./0.08 mm.

(b) 3-Benzoylbenzaldehyde (alternative preparation)

3-Benzoylbenzyl alcohol (2.0 g) in acetone (10 ml) was treated dropwise at 15°-20° C. with chromic acid solution. After stirring for 5 minutes, water (50 ml) was added and the mixture extracted with ether. The ethereal solution was washed with saturated Na₂ CO₃, saturated NaCl, dried (Na₂ SO₄), evaporated and distilled; b.p. 160°-170° C./0.08 mm, (1.1 g).

(c) (αRS)-Cyano-3-benzoylbenzyl alcohol

3-Benzoylbenzaldehyde (1.0 g) in dioxan (5 ml) was treated with water (2.5 ml) and sodium cyanide (0.5 g). The whole was cooled below 15° C. and 40% sulphuric acid (1.4 ml) added dropwise (care being taken to ensure that this temperature was not exceeded). Stirring was continued for 1 hour when water (30 ml) was added and the product extracted with methylene chloride and washed with water, saturated NaCl, dried over Na₂ SO₄ and evaporated.

Yield=1.1 g; n_(D) =1.5996.

EXAMPLE 37

3-Benzoylbenzyl alcohol

3-Methylbenzophenone (52 g), N-bromosuccinimide (63 g) and dry carbon tetrachloride (1,000 ml) were heated at reflux for 8 hours when the mixture was cooled, filtered and the filtrate evaporated to yield the crude bromide. Sodium acetate (32.6 g) and acetic acid (300 ml) were added and the whole heated at reflux for 6 hours, poured into water (1,000 ml) and extracted with ether (1,000 ml). The ethereal solution was washed with water (2×300 ml), saturated sodium carbonate solution and saturated sodium chloride solution, dried (Na₂ SO₄), evaporated and fractionally distilled yielding the acetate (10.5 g), b.p. 138°-140° C./1 mm n_(D) =1.5789.

Lower boiling fractions containing the corresponding aldehyde were treated with sodium metabisulphite solution to remove the compound combined with the above acetate and refluxed for 2 hours with sodium hydroxide (3.0 g) in methanol (4.0 ml). The solution was poured onto water (200 ml), extracted with ether (2×200 ml) and the ethereal solution washed with saturated NaCl (2×100 ml), dried over Na₂ SO₄, evaporated and distilled to give the required alcohol b.p. 168°-170° C./1 mm (10.0 g) n_(D) =1.6165.

EXAMPLE 38

(1R)cis-2,2-dimethyl-3-(2,2-dibromovinyl)-cyclopropane carboxylic acid was prepared by the procedure described in Example 27. A solution of the acid (1 m.mole) in benzene (10 ml) was treated with an equivalent amount of pyridine and thionyl chloride and the mixture left to stand at room temperature for two hours. A solution of pyridine (98 mg) 3-benzoylbenzyl alcohol (210 mg) and in dry benzene (2 ml) was then added to the solution containing the carboxylic acid chloride and the mixture left to stand overnight. The next morning, the solution was run through a chromatograph column of neutral alumina and the solution containing the ester evaporated to dryness to give 3-benzoylbenzyl(1R)cis-2,2-dimethyl-3-(2,2-dibromovinyl)cyclopropane carboxylate (400 mg) n_(D) ²⁰ 1.5939. This compound is designated P39A.

EXAMPLE 39

The procedure described in Example 38 was repeated but using (1RS)-trans-2,2-dimethyl-3-(2,2-dichlorovinyl)cyclopropane carboxylic acid described in Example 18, (1R)trans and (1R)cis-2,2-dimethyl-3-(2,2-difluorovinyl)cyclopropane carboxylic acid described in Examples 29 and 30 to give:

3-benzoylbenzyl(1RS)-trans-2,2-dimethyl-3-(2,2-dichlorovinyl)cyclopropane carboxylate, n_(D) ²⁰ 1.5722, Compound P39B;

3-benzoylbenzyl (1R)trans-2,2-dimethyl-3-(2,2-difluorovinyl)cyclopropane carboxylate, n_(D) ²⁰ 1.5478: Compound P39C;

3-benzoylbenzyl (1R)-cis-2,2-dimethyl-3-(2,2-difluorovinyl)cyclopropane carboxylate, n_(D) ²⁰ 1.5507, Compound P39D.

EXAMPLE 40

The procedure described in Example 38 was repeated but using, as the alcohol, (αRS)-cyano-3-benzoylbenzyl alcohol prepared as described in Example 36 to give the following esters:

(αRS)-cyano-3-benzoylbenzyl (1R)cis-2,2-dimethyl-3-(2,2-dibromovinyl)-cyclopropane carboxylate, n_(D) ²⁰ 1.5800, Compound P39E,

(αRS)-cyano-3-benzoylbenzyl (1RS)-trans-2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropane carboxylate, n_(D) ²⁰ 1.5593, Compound P39F,

(αRS)-cyano-3-benzoylbenzyl (1R)-trans-2,2-dimethyl-3-(2,2-difluorovinyl)-cyclopropane carboxylate, n_(D) ²⁰ 1.5437, Compound P39G and

(αRS)-cyano-3-benzoylbenzyl (1R)-cis-2,2-dimethyl-3-(2,2-difluorovinyl)-cyclopropane carboxylate, n_(D) ²⁰ 1.5450, Compound P39H.

Acaricidal activity has been measured by injecting solutions of test compound P39E into engorged female ticks, Boophilus microplus, Biarra strain and the ability of the female to lay eggs 14 days after injection determined. The results are expressed as a percent of inhibition of egg laying ability compared to untreated control ticks. The following results were obtained:

    ______________________________________                                                 % Inhibition                                                                   Concentration of test compound                                         Compound  10 mg/ml    1 mg/ml  0.1 mg/ml                                       ______________________________________                                         P39E      100         90       0                                               ______________________________________                                    

Experiments to compare the relative toxicity (LD₅₀) of compound P39E with certain related compounds have been carried out towards both Ephestia kuhniella and Venturia canescens so that the relative toxicity to the two species can be calculated. The ratio of the selective toxicity to Ephestia compared to Venturia shows a measure of the selectivity of the agent and the higher this selectivity, the more effective is the compound in killing Ephestia without killing its parasite Venturia. The selectivities found were as follows:

    ______________________________________                                         Compound                   Selectivity                                         ______________________________________                                         Compound P39E                  7.9                                             3-Phenoxybenzyl-(1R)-trans-                                                                      (Compound P29M                                                                              2.8                                             2,2-dimethyl-3-(2,2-dichloro-                                                                    of Example 32)                                               vinyl)cyclopropanecarboxylate                                                  3-Phenoxybenzyl(1R)-cis-                                                                         (Compound P29L                                                                              2.3                                             2,2-dimethyl-3-(2,2-dichloro-                                                                    of Example 32)                                               vinylcyclopropanecarboxylate                                                   (αS)-cyano-3-phenoxybenzyl-                                                                (S) isomer of                                                                               3.6                                             (1R)-cis-2,2-dimethyl-3-                                                                         Compound P29B                                                (2,2-dibromovinyl)cyclopropane-                                                                  of Example 27)                                               carboxylate                                                                    ______________________________________                                    

These results show a very marked and quite unexpected selectivity in favour of compound P39E.

EXAMPLE 41

3-Phenoxybenzyl(1RS)-trans-2,2-dimethyl-3-(2,2-dichlorovinyl)cyclopropane carboxylate

(1RS)-Trans-2,2-dimethyl-3-(2,2-dichlorovinyl)cyanopropane carboxylic acid (1.0 g, 0.0048M), m-phenoxybenzyl alcohol (1.0 g, 0.0050M) and para-toluene sulphonic acid (0.01 g) in toluene (100 ml) were refluxed with a Dean and Stark take-off for 36 hours. On cooling, the solution was extracted with 5% aqueous sodium bicarbonate (2×50 ml), then water (2×50 ml), dried over anhydrous sodium sulphate and evaporated in vacuo. The residue was passed down an acid washed alumina column using petroleum ether (b.p. 80°-100° C.) as eluant. On evaporation of the solvent, this yielded the title compound as a colourless oil which crystallised on standing.

The following formulations are given to illustrate the way in which the insecticidal compounds of the invention can be applied to insects or environments susceptible to insect attacks.

    ______________________________________                                         Formulation 1                                                                  Oil-based liquid spray for household insects                                   ______________________________________                                         active compound       0.015% w/v                                               25% Pyrethrum Extract 0.25%                                                    Piperonyl butoxide    0.5%                                                     Antioxidant           0.1%                                                     ______________________________________                                    

Odourless light oil solvent e.g. xylene to make 100 vols.

    ______________________________________                                         Formulation 2                                                                  Water-based liquid spray concentrate for mosquito control                      ______________________________________                                         active compound       0.25% w/v                                                Piperonyl butoxide    1.0%                                                     Non-ionic emulsifier  0.25%                                                    Antioxidant           0.1%                                                     Water to make         100 vols.                                                ______________________________________                                    

This concentrate should be diluted 1:80 v/v with water before spraying.

    ______________________________________                                         Formulation 3                                                                  Aerosol                                                                        ______________________________________                                         active compound           0.05% w/v                                            25% Pyrethrum Extract     0.8%                                                 Piperonyl butoxide        1.5%                                                 Odourless petroleum distillate (b.p.                                                                     17.338%                                              200-265°)                                                               Propellant, e.g. a mixture of equal                                                                      80.0%                                                quantities of trichloromonofluoromethane                                       and dichlorodifluoromethane                                                    Perfume                   0.2%                                                 Antioxidant               0.1%                                                 ______________________________________                                    

    ______________________________________                                         Formulation 4                                                                  Mosquito coil                                                                  ______________________________________                                         active compound          0.25% w/w                                             Tabu powder (also known as pyrethrum                                                                    30.0%                                                 marc)                                                                          Filler(s), e.g. wood flour, powdered                                                                    68.75%                                                leaves or nut shells                                                           Brilliant Green          0.5%                                                  p-Nitrophenol            0.5%                                                  ______________________________________                                    

    ______________________________________                                         Formulation 5                                                                  Emulsifiable concentrate                                                       ______________________________________                                         active compound        1.5% w/w                                                Non-ionic emulsifier   25.0%                                                   Xylene                 73.4%                                                   Antioxidant            0.1%                                                    ______________________________________                                    

This concentrate may then be diluted at the rate of 30 mls. to 41/2 liters of water prior to use.

    ______________________________________                                         Formulation 6                                                                  General purpose powder for household, garden, livestock                        or grain storage use                                                           ______________________________________                                         active compound           0.05% w/w                                            Tropital (the synergist piperonyl-bis-                                                                   0.25%                                                2-[2'-n-butoxyethoxy]ethyl acetal)                                             Antioxidant, e.g. butyl hydroxy toluene or                                                               0.03%                                                butyl hydroxy anisole                                                          Filler                    99.67%                                               ______________________________________                                    

The insecticidal activity of the esters of the invention was assessed against houseflies and mustard beetles using the following techniques:

Houseflies (Musca domestica)

Female flies were treated on the thorax with a one microliter drop of insecticide dissolved in acetone. Two replicates of 15 flies were used at each dose rate and 6 dose rates were used per compound under test. After treatment, the flies were maintained at a temperature of 20° C.±1° and kill was assessed 24 and 48 hours after treatment. LD₅₀ values were calculated in micrograms of insecticide per fly and relative toxicities were calculated from the inverse ratios of the LD₅₀ values. (see Sawicki et al, Bulletin of the World Health Organisation, 35,893, (1966) and Sawicki et al, Entomologia and Exp. Appl. 10, 253, (1967)).

Mustard Beetles (Phaeden cochleariae Fab)

Acetone solutions of the test compound were applied ventrally to adult mustard beetles using a micro drop applicator. The treated insects were maintained for 48 hours after which time kill is assessed. Two replicates of 40 to 50 mustard beetles were used at each dose level and 3 to 4 dose levels were used for each compound. Again, LD₅₀ values were calculated and relative toxicities were calculated for the inverse ratios of LD₅₀ (see Elliott et al, J. Sci. Food Agric. 20, 561, (1969)).

Relative toxicities were calculated by comparison with 5-benzyl-3-furylmethyl (1R)-trans-chrysanthemate which is one of the most toxic chrysanthemate esters known to houseflies and mustard beetles, its toxicity being about 24 times that of allethrin to houseflies and 65 times that of allethrin to mustard beetles.

The following relative toxicities were obtained.

    ______________________________________                                         Relative Toxicity                                                              Compound         Houseflies                                                                               Mustard Beetles                                     ______________________________________                                         5-benzyl-3-furylmethyl                                                                          1000      1000                                                (1R)-trans-chrysanthemate                                                      Pyrethrin I      12        1600                                                Bioallethrin     60        20                                                  A                1700      2000                                                B                630       890                                                 C                270       420                                                 F                21        --                                                  G                18        --                                                  H                <7        10                                                  I                <7        <10                                                 K                1300      1600                                                Q                60        69                                                  R                30        300                                                 S                120       170                                                 T                240       300                                                 P19A             91        100                                                 P19B             67        320                                                 P19C             24        40                                                  P19D             290       440                                                 P19E             290       500                                                 P19F             130       360                                                 P19G             300       500                                                 P19H             20        50                                                  P21A             2500      2700                                                P21B             1100      1900                                                P21C             1000      2200                                                P21D             1200      1700                                                P21E             700       1800                                                P21F             400       790                                                 P21G             680       780                                                 P21H             660       740                                                 P21I             170       420                                                 P21J             360       350                                                 P21K             340       350                                                 P21M             19        370                                                 P21N             100       2000                                                P21P             1300      5000                                                                 at least                                                      P24A             82        310                                                 P24B             150       310                                                 P24C             53        120                                                 P24D             450       290                                                 P29A             2200      1600                                                P29B             10000     11000                                               P29B (crystalline isomer)                                                                       23000     14000                                               P29B (non-crystalline isomer)                                                                   3500      4000                                                P29C             1100      4000                                                P29D             4100      5200                                                P29E             3900      3100                                                P29F             1700      --                                                  P29G             3800      2400                                                P29H             1800      750                                                 P29J             11000     4200                                                P29K             140       130                                                 P29L             1600      1400                                                P29M             740       2100                                                P29N             2600      2200                                                ME3              150       30                                                  ME4              60        70                                                  ME5              300       40                                                  ME6              390       50                                                  P31A             3900      1900                                                P31B             620       270                                                 P31C             840       730                                                 P31D             2300      1300                                                P31E             1800      850                                                 P31F             1200      2200                                                P39A             50        830                                                 P39B             10        590                                                 P39C             6         50                                                  P39D             20        500                                                 P39E             330       2200                                                P39F             80        600                                                 ME7              1100      5000                                                ME8              140       265                                                 ME9              50        50                                                  ME10             40        30                                                  ______________________________________                                    

The relative toxicity of compounds P21Q and P21S were measured against houseflies by the turntable method, they were found to have toxicities of 13 mg/100 ml and 200 mg/100 ml respectively and against German cockroaches, by the topical application method, they were found to have toxicities of 6.78 γ/insect and 5.08 γ/insect respectively. These figures are to be compared with 200-300 mg/100 ml and 0.8 to 1.4 γ/insect respectively for natural pyrethrin. Mammalian toxicity of certain esters of the invention has been determined in rats with the following results:

    __________________________________________________________________________                              LD.sub.50 (mg/kg) to rats                                      Compound        oral   intravenous                                    __________________________________________________________________________              Pyrethrin I     260-420                                                                               2-5                                                     5-benzyl-3-furylmethyl                                                                         >8000  340                                                     (1R)-trans chrysanthemate                                                      A                800-1000                                                                             120                                                     P21 E             40    5                                                      P21 C            >400  26-33                                          __________________________________________________________________________     The insecticidal activity and mammalian toxicity of certain esters of          (1RS)-trans-2,2-dimethyl-3-(2,2-                                               dichlorovinyl)-cyclopropane carboxylic acid has been tested in a further       series of experiments                                                          with the following results:                                                                       Insecticidal activity                                                                          Mammalian toxicity                                                     German  oral acute LD.sub.50 mg/kg                  R                  Houseflies*.sup.1                                                                      Cockroaches*.sup.2                                                                     Rats    Mice                                __________________________________________________________________________      ##STR14##         10.5 mg/100 ml.                                                                        0.83γ/insect                                                                     >300    >300                                 ##STR15##         55 mg/ 100 ml.                                                                         4.2γ/insect                                                                      --      --                                   ##STR16##         13 mg/100 ml.                                                                          6.7γ/insect                                                                      300     approxi- mately   300                ##STR17##         4.5 mg/100 ml                                                                          0.54γ/insect                                                                     --        100                                                  Pyrethrin:                                                                             5-benzyl-3-     Pyrethrin                                              200-300 mg/                                                                            furyl-methyl    130                                                    100 ml. (1RS)-cis-trans-                                                               chrysanthemate.                                                                0.62γ/insect                                                             Pyrethrin:                                                                     0.8-1.4γ/insect                               __________________________________________________________________________      *.sup.1 turn table method                                                      *.sup.2 topical application method                                       

The synergisability of certain esters of the invention has been determined in tests in which the LD₅₀ of the insecticide in μg. per female fly was determined by the above described methods in untreated flies and in flies pretreated with 2 μg. per fly of the synergist sesamex (2-(3,4-methylene dioxyphenoxy)-3,6,9-trioxa undecane). The following results are obtained

    ______________________________________                                                   LD.sub.50                                                                        active                  Approx.                                                compound  active compound +                                                                            Synergis-                                  Active compound                                                                            only      synergist     tic factor                                 ______________________________________                                         5-benzyl-3-furyl                                                                           0.0054    0.00057       9.4                                        methyl (1R)-trans-                                                             chrysanthemate                                                                 5-benzyl-3-furyl                                                                           0.010     0.00079       13                                         methyl(1RS)-cis-                                                               trans-                                                                         chrysanthemate                                                                 P21C        0.0065    0.00033       19                                         P21D        0.0058    0.00046       12                                         P21F        0.013     0.00033       39                                         P21G        0.0083    0.00037       22                                         A[(1R)-trans-(3-                                                                           0.0042    0.00033       13                                         cis-but-1-enyl)-                                                               isomer]                                                                        A[(1R)-cis-(3-cis-                                                                         0.0074    0.0012        6                                          but-1-enyl)-isomer]                                                            ______________________________________                                    

By repeating the above synergisability test but pretreating flies instead with 5 micrograms per fly of the synergist Sesamex 3 hours before applying the pyrethroid, the following results were obtained:

    ______________________________________                                                  LD.sub.50 in μg                                                               Active    Active compound                                                                             Approx.                                                 compound  (flies pretreated                                                                           synergist                                    Active compound                                                                           only      with synergist)                                                                             factor                                       ______________________________________                                         P21P       0.0073    0.00088      8.3                                          P29B (S) isomer                                                                           0.0016    0.00023      7                                            ______________________________________                                    

The insecticidal activity of the compounds of the invention may also be synergised by formulation with other compounds known to be capable of synergising natural pyrethrin and synthetic pyrethroids. Such synergists include piperonyl butoxide (3,4-methylenedioxy-6-propylbenzyl butyl-diethylene glycol ether); Tropital (piperonyl-bis-2-(2'-n-butoxyethoxy]ethyl acetal); sulphoxide [1,2-methylenedioxy-4-(2-octylsulphinyl)propyl)-benzene]; propylisome (di-n-propyl-2-methyl-6,7-methylenedioxy-1,2,3,4-tetrahydronaphthalene-3,4-dicarboxylate) and MGK264 [N-(2-ethylhexyl)-[2,2,1]-5-heptene-2,3-dicarboximide]. These synergists are desirably present in a ratio of 1:1 to 50:1 with respect to the pyrethroid, preferably 1:1 to 10:1.

Topical application of pyrethroids alone and in combination with synergist gave the following LD₅₀ results in micrograms with female Musca domestica:

    ______________________________________                                                             LD.sub.50 (μg)                                                                            LD.sub.50 (μg)                                    LD.sub.50 (μg)                                                                          Active compound +                                                                            Active                                       Active  Active      piperonyl     compound +                                   compound                                                                               compound only                                                                              butoxide (1:5)                                                                               Tropital (1:5)                               ______________________________________                                         P21H    0.031       0.018         0.019                                        P21E    0.044       0.022                                                      A (trans)                                                                              0.034       0.015                                                      ______________________________________                                     

We claim:
 1. A compound of the general formula: ##STR18## wherein R¹ represents hydrogen, R² represents hydrogen or halogeno, R³ represents halogeno and R represents a group of formula: ##STR19## wherein D represents H, CN or C.tbd.CH, Z³ represents 0, Z¹ and Z² independently represents chlorine or methyl and n=0, 1 or 2, there being at least one up to three chloro and/or methyl substituents present.
 2. A compound according to claim 1 wherein R² and R³ independently represent fluorine, chlorine or bromine.
 3. A compound according to claim 1 wherein at least one of R² and R³ is fluorine, chlorine or bromine and R¹ is hydrogen.
 4. A compound according to claim 1 wherein the hydrogen atoms at C₁ and C₃ on the cyclopropane ring are substantially completely in the trans configuration or in the cis configuration.
 5. An optically active compound according to claim 4 in the form of a (1R)cis isomer or a (1R)trans isomer.
 6. A compound according to claim 1 in the form of a (1RS)-cis,trans isomer mixture.
 7. A pesticidal composition comprising a compound according to claim 1 together with a diluent or carrier.
 8. A composition according to claim 7 including a pyrethrin synergist.
 9. A composition according to claim 7 including natural pyrethrin or a component thereof or another synthetic pyrethroid.
 10. A method of pest control which comprises applying to a pest or an environment susceptible to pest attack a compound according to claim
 1. 